societat catalana d’immunologia (sci) · dr. lluis santamaria (universitat de barcelona, spain)...

XII CONGRÉS

Societat Catalana d’Immunologia (SCI)

Programa Final

Barcelona, 15 i 16 de Novembre de 2018

Noves Perspectives en Malalties Inflamatòries Cròniques

New Perspectives in Chronic Inflammatory Diseases

2 www.sci.cat

Organization Committee (SCI Board):

Welcome to the Congress,

On behalf of the organising committee, we would like to warmly welcome you to the

XIIth Societat Catalana d’Immunologia Congress (SCI congress). We make every effort to

ensure the excellence of the scientific content and that young researchers will have the

opportunity to present and discuss their data.

Dr. Ricardo Pujol Borrell

SCI President

XIIth Congress of the Catalan Society of Immunology: New Perspectives in Chronic Inflammatory Diseases has been accredited by the Catalan Lifelong Learning Board of the Healthcare Professions with 5,5h (Record: 09/023488-MD).

President: Dr. Ricardo Pujol Borrell Vice President: Dra. Annabel Valledor Fernández Secretary: Dr. Francesc Rudilla Salvador Member & Acting Treasurer: Dra. Aina Teniente Serra Member: Dr. Jordi Bas Minguet Member: Dra. Virgínia Mas Bosch Member: Dra. M. Esther Moga Naranjo

Congress Office: Sr.Xavier Nieves ([email protected])

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This Congress is sponsored by:

Gold Sponsor

Silver Sponsors

Sponsors

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Content

This Congress is sponsored by: ........................................................................................... 3

Content ................................................................................................................................ 4

Scheme first day .................................................................................................................. 5

Scheme second day ............................................................................................................ 6

Corporative Abbreviations .................................................................................................... 8

Abstracts .............................................................................................................................. 9

Oral Communications Session I .................................................................................. 9

Clinical Immunology 1 - 5 ................................................................................................. 9

Oral Communications Session II Innate Response 6 - 10 ........................................ 14

Oral Communications Session III From Innate to Adaptative Immunity 11 - 16 ........ 19

e-poster List ....................................................................................................................... 25

Posters Clinical Immunology 1 - 19 ................................................................................ 25

Posters Diagnostic Immunology 20 - 21 ......................................................................... 44

Posters Immune Response 22 - 28 ................................................................................ 46

Posters Innate Immunity 29 ............................................................................................ 53

2019 Events ....................................................................................................................... 54

Lifelong Learning SCI Program 2019 ............................................................................. 54

New members Registration form to SCI ............................................................................. 55

Participant information: useful information ......................................................................... 56

List of participants and authors .......................................................................................... 57

Other useful information and notes .................................................................................... 60

Awards to the best communication and to the best poster at the XII Congress SCI 2018, sponsored by SCI

This year SCI sponsors the awards for the best communication (250 €) and for the best poster (100 €) of this congress.

The Chairpersons of the different sessions of the congress and the board members of the SCI will select the best oral

communications presented, taking into account its scientific value and the aspects related to the presentation. The poster

awarded will be chosen by the congress attendees activating the electronic vote inside the electronic panels of the

posters. The results will be announced at the end of the congress.

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Scheme first day

Thursday, November 15th

15:30 16:00

Arrival, Registration and Documentation delivery

16:00 16:05

Welcome to the XIIth CONGRESS of SCI Dr. Ricardo Pujol Borrell (President of SCI)

16:05 17:00

Chair: Dra. Silvia Vidal (IRHUSCSP)

Dr. OLIVER SÖHNLEIN (Ludwig-Maximilians-University of Munich, Germany)

Neutrophils in atherosclerosis: from physiology to intervention

17:00 17:30

Poster viewing – Coffee Break Posters can be viewed on the 4 electronic panels located in the Hall

17:30 18:30

Chair: Dra. Eva Mª Martínez-Cáceres (HUGTiP)

Dr. LLUIS SANTAMARIA (Universitat de Barcelona, Spain)

CLA+ T lymphocytes in psoriasis

18:30 19:45

Oral Communications Session I: Clinical Immunology

Chairs: Dra. Eva Mª Martínez-Cáceres (HUGTiP) and Dra. Virgínia Mas (HUBell) 18:30h Academic development and application of a CART19 in our environment: ARI-0001. M.

Juan et al. (oral presentation 1).

18:45h Serum uromodulin, a new biomarker of renal function? C. Esteve Cols et al. (oral

presentation 2). 19:00h Identificació d'un mòdul genètic associat a la resposta clínica al tractament anti-TNF en

Artritis Reumatoide mitjançant un anàlisi multi-òmic. A. Aterido et al. (oral presentation 3). 19:15h Th1-skewed profile and excessive production of proinflammatory cytokines in a NFKB1-

deficient patient with CVID and severe gastrointestinal manifestations. R. Dieli-Crimi et al. (oral presentation 4).

19:30h Newborn screening (nbs) program experience for Severe Combined Immunodeficiency

(SCID) diagnostic in Catalonia. M. García-Prat et al. (oral presentation 5).

19:45 End of session

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Scheme second day

Friday, November 16th

08:30 08:55

Arrival, Registration and Documentation delivery

09:00 10:00

Chair: Dr. Josep Saura (Institut de Neurociències, UB)

Dra. ANNA MARIA PLANAS (IIBB-CSIC, Barcelona)

Responses of microglia and brain infiltrating leukocytes to acute stroke

10:00 11:00

Oral Communications Session II: Innate Response

Chair: Dra. Silvia Vidal (IRHUSCSP) and Dr. Francisco Lozano (HCB, UB)

10:00h Immunomonitoring of CD64 and HLA-DR biomarkers in ICU patients with high risk of

developing sepsis. Predictive, diagnostic and prognostic study. E. Lucas Varas et al.

(oral presentation 6).

10:12h Type I interferonopathies, macrophages, Samhd1 and RNase H2. T. Vico et al. (oral

presentation 7).

10:24h TNFAIP3 haploinsufficiency is the cause of autoinflammatory manifestations in a patient

with a deletion of 13Mb on chromosome 6. C. Franco-Jarava et al. (oral presentation 8).

10:36h Interferonopathies and macrophages: regulation of MDA5 expression. A. Celada et al.

(oral presentation 9).

11:48h Prenatal betamethasone protects against experimental Type 1 Diabetes by modulating

both immune system development and β-cells. D. Perna-Barrull et al. (oral presentation

10).

11:00 11:30


11:30 12:30

Chair: Dr. Francesc Borràs (IGTP)

Dr. CARLOS MINUTTI (The Francis Crick Institute, London, UK)

Tissue-specific signals that modulate IL-4Rα–mediated macrophage activation in lung repair

12:30 13:30

Ordinary General Meeting / Junta General Ordinària SOCIETAT CATALANA d’IMMUNOLOGIA (SCI) (12:30h – First Call) Us hi esperem a tots: els socis i no-socis!!

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13:30 15:00

Poster viewing – LUNCH Posters can be viewed on the 4 electronic panels located in the Hall

15:00 16:30

Oral Communications Session III: From Innate to Adaptative Immunity

Chair: Dr. Rosa Faner (CIBERES, HCB) and Dra. Cristina Costa (IDIBELL)

15:00h Comparing the efficiency of two clinical grade stimuli on BDCA3+ mDCs by using

transcriptomics for immunotherapy. G. Flórez Grau et al. (oral presentation 11).

15:15h Gene Expression Profile of Tolerogenic Dendritic Cells Differentiated with Vitamin D3,

Dexamethasone and Rapamycin. J. Navarro-Barriuso et al. (oral presentation 12).

15:30h Optimal response to dimethyl fumarate is mediated by a reduction of th17.1 cells after 3

months of treatment. Mª. J. Mansilla et al. (oral presentation 13).

15:45h Anti-Ly9 (CD229) targeting depletes marginal zone B cell and prevents salivary gland

infiltration in a mouse model of Sjögren's Syndrome. J. Puñet-Ortiz et al. (oral presentation

14).

16:00h Decreased IFN-γ production in umbilical cord blood is associated with Breg cells. A.

Esteve-Solé et al. (oral presentation 15).

16:15h Low mucosal microbial load favors fecal microbiota colonization and anti-inflammatory

response. G. Sarrabayrouse et al. (oral presentation 16).

16:30 17:00


17:00 18:00

Chair: Dra. Dolores Jaraquemada (IBB, UAB)

Dr. ANDREAS RAMMING (Universitätsklinikum Erlangen, Erlangen, Germany)

Type 2 innate lymphoid cells and resolution of inflammation

18:00 18:30

Chair: Dra. Dolores Jaraquemada (IBB, UAB)

Drs. ANDREAS RAMMING, CARLOS MINUTTI, LLUIS SANTAMARÍA

ROUND TABLE: ILCs as a bridge between Innate and Adaptive Immunity

18:30 18:45

Prize to the best communication and poster Dr. Ricardo Pujol Borrell (President of SCI).

End of Congress

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Corporative Abbreviations BST Banc de Sang i Teixits

CDB Centrede Diagnòstic Biomèdic

CIBER-BBN Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina

CIBERDEM Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas

CIBER-ER Centro de Investigación Biomédica en Red de Enfermedades Raras

CIBERES Centro de Investigación Biomédica en Red de Enfermedades Respiratorias

CIBERONC Centro de Investigación Biomédica en Red de Oncología

CSIC Consejo Superior de Investigaciones Científicas

HCB Hospital Clínic de Barcelona HSCSP Hospital de la Santa Creu i Sant Pau

HSJD Hospital Sant Joan de Déu

HUBell Hospital Universitari de Bellvitge

HUGTiP Hospital Universitari Germans Trias i Pujol

HUVH Hospital Universitari Vall d’Hebron

IBB Institut de Biotecnologia i Biomedicina

ICMD Institut Clínic de Medicina i Dermatologia

ICREA Institució Catalana de Recerca i Estudis Avançats

IDIBAPS Institut d'Investigacions Biomèdiques August Pi i Sunyer

IDIBELL Institut d'Investigació Biomèdica de Bellvitge

IGTP Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol

IIBB Institut d'Investigacions Biomèdiques de Barcelona- INSA Institut de Recerca en Nutrició i Seguretat Alimentària

IRB Lleida Institut de Recerca Biomèdica Lleida

IRHUSCSP Institut de Recerca Hospital Universitari de la Santa Creu i Sant Pau IRSJD Institut de Recerca Sant Joan de Déu

ISCIII Instituto de Salud Carlos III

SCI Societat Catalana d’Immunologia

UAB Universitat Autònoma de Barcelona

UB Universitat de Barcelona

UPIIP Unitat Pediatrica de Malalties Infeccioses i Immunodeficiències Primaries

VHIR Vall d’Hebron Institut de Recerca

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Abstracts

Oral Communications Session I Clinical Immunology 1 - 5

1 Academic development and application of a CART19 in our

environment: ARI-0001

Juan, Manel1,2,3,4

; Castella, Maria3; Boronat, Anna

3; Caballero, Miguel

1,2; Ortiz-Maldonado, Valentín

1,3;

Rodríguez, Vanina3; Martín-Ibáñez, Raquel

4; Suñe, Guillermo

3; Perpiña, Unai

6; Marzal, Berta

3;

Castaño, Julio5; Bueno, Clara

5; Balagué, Olga

1; González-Navarro, E. Azucena

1; Serra-Pagés, Carles

1;

Engel, Pablo4; Vilella, Ramon

4; Benítez, Daniel

1,3; Cid, Joan

1; Tabera, Jaime

7; Canals, Josep Mª

4,6;

Lozano, Miquel1; Baumann, Tycho

1; Vilarrodona, Anna

7; Trias, Esteve

1,7; Campo, Elías

1,3; Menéndez,

Pablo5; Urbano-Ispizua, Álvaro

1,3,4,5; Yagüe, Jordi

1,3,4; Pérez-Galán, Patricia

3; Rives, Susana

2; Delgado,

Julio1,3,5

; más de 100 profesionales adicionales1,2

.

1Hospital Clínic de Barcelona;

2Hospital Sant Joan de Déu;

3IDIBAPS;

4Universitat de Barcelona;

5Institut

Josep Carreras; 6Creatio;

7Banc de Sang i Teixits

The therapy with genetically modified T-cells with anti-CD19 Chimeric Antigen Receptors

(CART19) has recently been incorporated as a therapeutic option against leukemias and

B-cell lymphomas. After preclinical development, and authorization by AEMPS (Spanish

drug agency) of our own CART19 product (ARI-0001), Hospital Clínic de Barcelona and

Hospital Sant Joan de Déu are developing their own clinical trial (CART19-BE-01,

NCT03144583, EudraCT 2016-002972-29). To date, 22 patients with acute lymphoblastic

leukemia, 4 non-Hodgkin lymphoma and 1 chronic lymphocytic leukemia has been treated.

Although safety is similar to those described results by other CART19 approaches, a

longer follow-up before closing the trial is necessary to establish any evaluation of efficacy.

A recently approved project for developing a phase II multicenter clinical trial will be the

base and next step to arrive to use this product for our patients in Spain. This preclinical

and clinical work shows that under an academic approach, development of a CART

program is feasible and, in general, equivalent to other commercial proposals.

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Oral Communications Session I

Clinical Immunology 1 - 5

2 Serum uromodulin, a new biomarker of renal function?

Clara Esteve Cols1,2

; Fredzzia-Amanda Graterol Torres3; Maruja Isabel Navarro Díaz

3; Àlex Soriano

Martínez1; Jordi Ara del Rey

3; Eva Mª Martínez-Cáceres

1,2; Bibiana Quirant-Sánchez

1,2

1Immunology Department Hospital Germans Trias i Pujol, Badalona, Spain;

2Department of Cell Biology,

Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra; 3Nephrology Department

Hospital Universitari Germans Trias I Pujol, Badalona, Spain.

Background: Membranous GlomeruloNephritis (MGN) and IgA Nephropathy (IgAN) are

the leading forms of primary glomerulonephritis. MGN is caused by autoantibodies against

PhospholipaseA-2 receptor, and IgAN by partially degalactosilated IgA1 (Gd-IgA1) that

induces the generation of immunocomplexes of soluble IgA receptor (CD89) and Gd-IgA1.

The glycoprotein uromodulin is synthesized exclusively in the ascending limf of loop of

henle. A decrease in serum values is a sensitive marker of low renal fucntion.

Objectives: We aim to evaluate serum uromodulin as a biomarker of renal function in

comparison to serum creatinine, renal glomerular filtrate (eGFR) and proteinuria.

Methodology: A retrospective study of 46 MGN, 22 IgAN patients diagnosed by renal

biopsy and 9 healthy Subjects (HS) was performed. Clinical and pathological features

were collected and analyzed according to sèrum uromodulin levels. Analysis of serum

uromodulin was performed with uromodulin-ELISA kit (Euroimmun®).

Results: MGN and IgAN patients has lower levels of serum uromodulin than HS (MGN:

131 ± 74.31; IgAN: 91.79 ± 57.12; HS 224.9 ± 74.70 ng/mL). There were no differences

between uromodulin levels and patients age or gender. We stratified the pateints

according to histopathological features of renal biopsy. MGN patients with positive biopsy

for IgG4 deposits, showed a correlation between serum uromodulin-eGFR (p<0.0007,

r=0.62) and serum uromodulin-creatinine (p<0.0565, r=-0.38). The same results were

ovserved in those IgAN patients with more severe renal biopsy (p<0.0037, r=0.76;

p<0.0002, r=-0.87), respectively.

Conclusions: The inverse correlation observed between uromodlin levels and severity of

renal biopsy suggests that uromodulin might be a prognostic biomarker of renal function,

especially in IgAN patients.

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3 Identificació d’un mòdul genètic associat a la resposta clínica al

tractament anti-TNF en Artritis Reumatoide mitjançant un

anàlisi multi-òmic

Adrià Aterido1; Jesús Tornero

2; Franciso Blanco

3; Benjamín Fernández-Gutierrez

4; Antonio

González5; Juan D. Cañete

6; Joan Maymó

7; Mercedes Alperi-López

8; Alex Olivè

9; Héctor Corominas

10;

Víctor Martínez-Taboada11

; Isidoro González12

; Antonio Fernández-Nebro13

; Alba Erra14

; Simón

Sánchez-Fernández15

; María López-Lasanta1; Mireia López Corbeto

1; Raül Tortosa

1; Laia Cidó

16; Sara

Marsal1; Toni Julià

1

1Vall d'Hebron Hospital Institut de Recerca, Barcelona, Grup de Recerca de Reumatologia;

2Hospital Universitario de

Guadalajara, Servicio de Reumatología; 3INIBIC-Hospital Universitario A Coruña,Servicio de Reumatología;

4Hospital

Clínico San Carlos, Madrid, Servicio de Reumatología; 5Instituto de Investigación Sanitaria Hospital Clínico Universitario

de Santiago de Compostela; 6Hospital Clínic de Barcelona, Servicio de Reumatología;

7Hospital del Mar, Barcelona,

Servicio de Reumatología; 8Hospital Universitario Central de Asturias, Servicio de Reumatología;

9Hospital Universitari

Germans Trias i Pujol, Barcelona, Servicio de Reumatología; 10

Hospital Moisès Broggi, Barcelona, Servicio de

Reumatología; 11

Hospital Universitario Marqués de Valdecilla, Santander, Servicio de Reumatología; 12

Hospital

Universitario La Princesa, Madrid, Servicio de Reumatología; 13

UGC Reumatología, Instituto Investigación Biomédica

Málaga, Hospital Regional Universitario; 14

Hospital Sant Rafael, Barcelona, Servicio de Reumatología; 15

Hospital

General La Mancha Centro, Ciudad Real, Servicio de Reumatología; 16

Barcelona Supercomputing Centre, Life Sciences

Department, Barcelona.

Objectius: L’artritis reumatoide (AR), es una malaltia autoimmune prevalent caracteritzada per la

infiltració sinovial de cèl·lules immunitàries. Tot i que els fàrmacs anti-TNF han augmentat la

qualitat de vida dels pacients, ~30% no responen al tractament i els mecanismes responsables

són desconeguts. L’objectiu del estudi és identificar variants genètiques associades a la resposta

anti-TNF mitjançant un anàlisi multi-òmic.

Mètodes: Per tal d’identificar mòduls de co-expressió gènica associats a la resposta anti-TNF, es

va extreure l’ARN de 13 biòpsies sinovials reumatoide i es va determinar l’expressió. Es varen

identificar els mòduls utilitzant el mètode WGCNA i es va analitzar l’associació amb la resposta

anti-TNF, definida pels criteris EULAR. L’associació genètica dels mòduls amb la resposta es va

realitzar utilitzant una cohort espanyola de 348 pacients amb AR tractats amb anti-TNF i obtinguts

mitjançant l’IMID-Consortium. L’anàlisi es va efectuar utilitzant el programa PLINK. L’associació

dels mòduls significatius es va analitzar en una cohort independent de 2.706 pacients amb AR

tractats amb anti-TNF. La implicació funcional dels mòduls validats es va estudiar mitjançant

l’anàlisi d’enriquiment en vies biològiques i marques epigenètiques específiques de tipus cel·lular.

Resultats: En l’anàlisi de co-expressió es van identificar 148 mòduls, 15 dels quals mostraven una

associació significativa amb la resposta anti-TNF (P<0.05). Dos dels 15 mòduls resultaren

genèticament associats a la resposta a infliximab (P<0.033) i adalimumab (P<0.041) en la cohort

espanyola. Utilitzant la cohort independent, es va replicar l’associació del mòdul associat a la

resposta a adalimumab (P=0.01). Aquest mòdul va mostrà un enriquiment en gens del

metabolisme de nucleòtids (P=2.41e-05). En l’anàlisi epigenètic, es va objectivar que les marques

específiques de cèl·lules immunitàries estaven enriquides en variants del mòdul validat (P<0.05)

Conclusions: L’eficàcia del tractament anti-TNF en AR té un component genètic que és específic

de fàrmac.

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4 Th1-skewed profile and excessive production of

proinflammatory cytokines in a NFKB1-deficient patient with

CVID and severe gastrointestinal manifestations

Romina Dieli-Crimi1,2

; Mónica Martínez-Gallo1,2

; Clara Franco-Jarava1,2

; Maria Antolín3; Laura Blasco

3;

Ida Paramonov3; Maria E. Semidey

4; Antoni Álvarez Fernández

5; Xavier Molero

6; Julio Velásquez

6;

Andrea Martín-Nalda2,7

; Ricardo Pujol-Borrell1,2

; Roger Colobran1,2,3

1Immunology Division, Hospital Universitari Vall d’Hebron (HUVH), Vall d’Hebron Research Institute (V;

2Jeffrey Model Foundation Excellence Center, Barcelona, Catalonia, Spain;

3Area of Clinical and Molecular

Genetics, Hospital Universitari Vall d’Hebron (HUVH), Barcelona; 4Pathology Department, Hospital

Universitari Vall d’Hebron (HUVH), Barcelona; 5Pneumology Department, Hospital Universitari Vall d’Hebron

(HUVH), Barcelona; 6Exocrine Pancreas Research Unit, Department of Digestive Diseases, Hospital

Universitari Vall d'Hebron; 7Pediatric Infectious Diseases and Immunodeficiencies Unit (UPIIP), Hospital

Universitari Vall d’Hebron.

Monoallelic loss-of-function mutations in NFKB1 were recently recognized as the most

common monogenic cause of common variable immunodeficiency (CVID). The prototypic

clinical phenotype of NFKB1-deficient patients includes common CVID features, such as

hypogammaglobulinaemia and sinopulmonary infections, plus other highly variable

individual manifestations.

Here, we describe a patient with a profound CVID phenotype and severe gastrointestinal

manifestations, including chronic and recurrent diarrhoea. Using an NGS customized

panel of 323 genes related to primary immunodeficiencies, we identified a novel

monoallelic loss-of-function mutation in NFKB1 leading to a truncated protein (c.1149delT /

p.Gly384Glu*48). Interestingly, we also found a rare variant in NOD2 previously

associated with Crohn’s disease (p.His352Arg).

Our patient had hypogammaglobulinaemia with a small number of B cells, most of which

were naïve. The most noteworthy findings included marked skewing towards a Th1

phenotype in peripheral blood T cells and excessive production of proinflammatory

cytokines (IL-1b, TNF-α). The patient’s 6-year-old daughter, a carrier of the NFKB1

mutation, is clinically asymptomatic, but has started to show cellular and molecular

changes.

This case of NFKB1 deficiency appears to be a combination of immunodeficiency and a

hyperinflammatory state. The current situation of the patient’s daughter provides a glimpse

of the preclinical phase of the condition.

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5 Newborn screening (NBS) program experience for Severe

Combined Immunodeficiency (SCID) diagnostic in Catalonia

Marina García-Prat

1,2; Andrea Martín-Nalda

1,2; Jacques G. Rivière

1,2; Ana Argudo Ramírez

3; Jose Luis

Marín Soria3; Rosa Mª López Galera

3; Sonia Pajares García

3; Jose Manuel González de Aledo

3; Roger

Colobran2,4



; Manuel Hernández-González2,4

; Rosa Mª

Fernández Bardon6; Pere Soler-Palacín

1,2

1Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron(HUVH);

2Jeffrey Modell Excellence Centre. Barcelona, Spain.;

3Newborn screening laboratory. Hospital Clinic,

Barcelona, Catalonia, Spain.; 4Immunology Division, Hospital Universitari Vall d’Hebron (HUVH), Barcelona,

Spain.; 5Public Health Agency of Catalonia. Departament de Salut. Generalitat de Catalunya, Spain;

6Agencia de Salut Publica de Catalunya.

Background: Severe combined immunodeficiency (SCID), the most severe form of T cell

immunodeficiency, can be screened at birth through quantification of T cell receptor

excision circles (TRECs) in dried blood spot (DBS 1.5mm diameter). We describe the

results of the first 15 months of the SCID newborn screening (NBS) program in Catalonia,

Spain.

Methods: All babies born (NB) between January 2017 and March 2018 were prospectively

analyzed. The quantification of TRECs was carried out with the Enlite-Neonatal TREC kit

from PerkinElmer®, (Massachusetts,USA). In 2018 the retest cutoff was changed from 34

to 24 copies/μL, decreasing the retest rate from 3.34% to 0.69%. T, B and NK cell flow

cytometry (CD45RO/RA, T CD4+ and CD8+ HLA-DR, TCR repertoire αβ/γδ TCR) and

lymphocyte mitogen proliferation was performed in all patients.

Results: Of 82.641 NB screened, 17 tested positive.Eleven were female (54.5%). There

was no history of maternal immunosuppression. Median initial lymphocytes count was 3.95

x109/L (Interquartile range (IQR)=2.6-6.6x109/L) while initial median T-cell count was 2.49

x109/L (IQR =1.54-4.0 x109/L). Final diagnoses were: SCID (1/17), chylothorax (1/17),

22q11 DiGeorge syndrome (4/17), prematurity (1/17) and idiopathic lymphopenia (2/17).

The remaining patients (8/17) were considered false positive due to initial normal

lymphocyte count with normalization of TRECs between 3 and 6 months of life.

Conclusions: One SCID patient was diagnosed through the NBS program during this

period revealing an incidence of 1:82.641 births in Catalonia. Encountered diagnoses were

similar to those described in larger NBS SCID programs, thus confirming the uselfulness of

the protocol.

14 www.sci.cat

Oral Communications Session II Innate Response 6 - 10

6 Immunomonitoring of CD64 and HLA-DR biomarkers in ICU

patients with high risk of developing sepsis. Predictive,

diagnostic and prognostic study

Ester Lucas Varas1; Oriol Plans Galván

2; Fernando Arméstar Rodríguez

2; Bibiana Quirant Sánchez

1,3;

Eva Mª Martínez-Cáceres1,3

1Immunology Department, Laboratori Clínic de la Metropolitana Nord, Hospital Germans Trias i Pujol;

2Intensive Care Unit, Hospital Germans Trias i Pujol, Badalona (Spain);


Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra

Introduction: Immunologically the sepsis is characterized by a pro-inflammatory response

and an accompanying antiinflammatory response that lead to a state of immunoparalysis.

Objective: The goals are to evaluate the predictive, diagnostic and prognostic potential of

mHLA-DR and nCD64 in critical patients with high predisposition to nosocomial infection.

Methods: We conducted a prospective observational study over 5 months between ICU

and the immunology laboratory at Hospital Germans Trias i Pujol. Peripheral blood from 21

critical patients with high predisposition to nosocomial infection was analyzed. Expression

of mHLA-DR and nCD64 was assessed at different timepoints by flow cytometry for 15

days of follow-up.

Results: Sixty-seven percent of patients developed infection. Non-infected patients had

higher expression of mHLADR, higher percentage of mHLA-DR at 3 day of monitoring (p-

value<0.05) and higher HLA-DR index than infected patients. An optimum nCD64 cut-off

value of 98.5 MFI for diagnostic of sepsis (sensitivity: 80%, specificity: 80%) and sepsis

index>0.035 for diagnostic of sepsis (sensitivity: 80%, specificity: 80%) was found.

Patients with septic shock had a higher sepsis index at day 3 (p-value<0.05) than infected

patients. Moreover, sepsis index showed a positive correlation with APACHE (r=0.784;

pvalue< 0.001) and SOFA scores (r=0.537; p-value<0.05).

Conclusions: Our results indicate that the immunomonitoring of the expression of mHLA-

DRand the HLA-DR index could be a useful predictive biomarker for the development of

infection. Moreover, the analyses of nCD64 expression and sepsis index might be a useful

test to diagnose sepsis and could complement current laboratory markers to detect sepsis.

As a prognostic marker, a high sepsis index shows a trend towards a worse clinical

evolution and could have a prognostic value.

Keywords: Sepsis, SIRS, CARS, CD64, HLA-DR, Sepsis Biomarker

www.sci.cat 15

Oral Communications Session II

Innate Response 6 - 10

7 Type I interferonopathies, macrophages, Samhd1 and RNase H2

Tania Vico1; Núria Elias

1; Antonio Celada

1; Jorge Lloberas

1

1Biology of Macrophages,

, Departament de Biologia Cel·lular, Fisiologia i Immunlogia, Parc Cientific de

Barcelona, Universitat de Barcelona.

Type I interferonopathies are characterized by the sustained up-regulation of type I IFN

signaling, caused by disturbances in the intracellular nucleic acid metabolism or sensing

pathways. Aicardi-Goutières Syndrome (AGS) is a type I interferonopathy that induces

brain calcifications. Mutations in Samhd1 or RNase H2 genes have been described in

patients with AGS, which are implicated in the loss of function of these proteins. The

expression of Samhd1 and RNase H2 genes were related to tissues with high macrophage

infiltration. Interestingly, Samhd1 expression was induced in bone marrow derived

macrophages (BMDM) by pro-inflammatory stimuli (IFN-γ and LPS), but not by growth

factors (M-CSF and GM-CSF) or antiinflammatory agents (IL-4). As animal models we

used the knock-out of Samhd1 and the knock-in of Rnasah2c (R69W mutation) in which

the RNase activity decreased to 35%. Differentiation to BMDM in these models was not

altered. However, upon treatment of macrophages with pro-inflammatory activators we

detected signs of DNA damage, such as an increase of p21waf-1 expression and the

number of γ-H2AX nuclear focis. In brain and heart, as well as in macrophages, we

detected an increased level of Interferon Stimulated Genes (ISG) expression, a hallmark of

AGS. Finally, inducing experimental autoimmune encephalitis (EAE) in Samhd1-/- mice we

observed an increased severity and decreased survival. We demonstrated that Samhd1

restrained the autoimmunity response in mice. These results reveal that Samhd1 and

RNase h2 confer protection against DNA damage during inflammation in macrophages,

caused by the production of reactive oxygen species. DNA damage in macrophages and

its alterations could be the origin of the IFN production and development of

interferonopathies such as AGS.

16 www.sci.cat



8 TNFAIP3 haploinsufficiency is the cause of autoinflammatory

manifestations in a patient with a deletion of 13Mb on

chromosome 6

Clara Franco-Jarava1,2

; Hongying Wang3; Andrea Martín-Nalda

2,4; Daniel Álvarez de la Sierra

1; Marina

García-Prat2,4

; Domingo Bodet5; Vicenç García-Patos

5; Alberto Plaja

6; Francesc Rudilla

7; Victor

Rodríguez-Sureda8,9

; Laura García-Latorre8,10

; Ivona Aksentijevich3; Roger Colobran

1,2,6; Pere Soler-

Palacín2,4,11

1Immunology Department, Hospital Universitari Vall d'Hebron, Diagnostic Immunology, Vall d’Hebron Res;

2Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Spain;

3Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, USA;

4Pediatric

Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Infe; 5Dermatology

Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain; 6Genetics Department, Hospital

Universitari Vall d’Hebron, Barcelona, Spain; 7Banc de Sang i Teixits de Catalunya, Barcelona, Spain;

8Drug

Delivery and Targeting Group, Molecular Biology and Biochemistry Research Centre for Nanomedici; 9Networking Research Centre for Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), Instituto;

10Centre for Biomedical Network Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, M;

11Medicine Department, Universitat Autonoma de Barcelona (UAB), Barcelona, Spain.

Background: Systemic autoinflammatory diseases are conditions in which the inflammasome is

upregulated and there is an increased production of pro-inflammatory cytokines, like IL-1b or IL-8.

Defects on proteins of the inflammasome complex or in NFkB pathway are found to be responsible

of some monogenic autoinflammatory syndromes. However, autoinflammatory diseases can be

also multifactorial, like happens in various conditions like Behçet or Sweet syndromes, making

differential diagnosis often challenging. On the other hand, there is scarce literature about

autoinflammation in syndromic patients.

Objective: The aim of our study was to check if haploinsufficiency of A20, a regulatory protein of

NFkB encoded by the gene TNFAIP3, could be the cause of the autoinflammatory phenotype of a

12 year-old patient who, in addition to psychomotor and growth delay, presented with fevers,

neutrophilic dermatosis, and recurrent orogenital ulcers since his first year of life.

Methods and Results: A large deletion of 13Mb in chromosome 6 was detected by a comparative

genomic hybridation (CGH) array. The region deleted included 53 genes, from among which

TNFAIP3 stood out as candidate gene, since previously reported clinical cases resembled our

patient’s autoinflammatory phenotype. Stimulation of patient’s fibroblasts with 20ng/mL TNF

showed a clearly decreased A20 expression, and consequently, an increase in the phosphorylated

levels of JNK, IKK, P38, P65 and IKBa. Patient’s cells showed increased total K63-Ub levels, as

well as increased ubiquitinated RIP and NEMO levels.

Conclusion: A20 haploinsufficiency can explain the autoinflammatory phenotype observed in the

patient. Functional assays are mandatory before concluding a pathogenic defect, mainly in

previously undescribed mutations. CGH arrays should be the first diagnostic method for

comprehensive analysis of patients with syndromic features and immune dysregulation.

www.sci.cat 17



9 Interferonopathies and macrophages: regulation of MDA5

expression

Antonio Celada

1; Pere Rehues

1; Iris Aparici

1; Martí López-Serrat

1; Jorge Lloberas

1

1Biology of Macrophages,

, Departament de Biologia Cel·lular, Fisiologia i Immunlogia, Parc Cientific de

Barcelona, Universitat de Barcelona.

Type I interferonopathies are due to overproduction of type I IFN that initiate and sustain

autoimmunity and that are caused by disturbances in the intracellular nucleic acid

metabolism or in cytosolic nucleic acidsensing pathways. The elucidation of the underlying

genetic causes has revealed novel cell-intrinsic mechanisms that protect the organism

against inappropriate immune recognition of self-nucleic acids by cytosolic sensors such

as cGAS or MDA5 through metabolizing or processing of intracellular DNA or RNA.

Aicardi-Goutières Syndrome (AGS) is an interferonopathy inducing brain calcification. Gain

of function mutations in MDA5 gene are associated with AGS. MDA5 is highly induced in

bone marrow derived macrophages (BMDM) by pro-inflammatory stimuli such as cytokines

IFN-α and IFN-γ or TLR ligands such as LPS or poly(I:C), but not by growth factor or anti-

inflammatory agents (IL-4). The induction by IFN-α or LPS is produced at the level of

transcription since the Mda5 half-live before or after induction is very stable. Interestingly,

Stat1 is required for Mda5 induction by IFN-α or LPS. This together with the time course of

induction, that require at least 3 to 6 hours and the need of protein synthesis indicates that

is an intermediate gene that needs the synthesis of an intermediate protein for

transcription. Using transfections of vectors with the Mda5 promoter and luciferase as

indicator we map a region sensitive to LPS, INF-α or poly(I:C). This region contains an IRF

sequence which mutation abolish the Mda5 induction. In summary, we detected in

macrophages the mechanism that control MDA5 induction by pro-inflammatory agents.

The correct function of MDA5 may protect these cells during inflammation against DNA

damage, caused by the production of reactive oxygen species. The DNA damage in

macrophages could be at the origin of IFN production and the development of

interferonopathies such as AGS.

18 www.sci.cat



10 Prenatal betamethasone protects against experimental Type 1

Diabetes by modulating both immune system development and

β-cells

David Perna-Barrull1; Silvia Rodríguez-Fernández

1; Irma Pujol-Autonell

1; Anna Gieras

2; Rosa M.

Ampudia1; Adrian Villalba

1; Laura Glau

2; Eva Tolosa

2; Marta Vives-Pi

1,3

1Immunology Section, Germans Trias i Pujol Research Institute, UAB, Badalona, Spain;

2Department of

Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 3CIBERDEM, ISCiii,

Barcelona, Spain.

Environmental factors are crucial in the pathogenesis of type 1 diabetes (T1D). In this

sense, drugs administered prenatally could alter the development of the foetal immune

system, thus influencing autoimmunity. Betamethasone is a synthetic glucocorticoid

administered to women at risk of preterm delivery to improve newborn survival, and it

could modify self-tolerance. The aim of this study was to determine the effect of prenatal

betamethasone on T1D susceptibility.

An incidence study was performed in non-obese diabetic (NOD) mice offspring of

betamethasone-treated pregnant females. T cell receptor Vβ repertoire was assessed

(flow cytometry) in prediabetic adult mice. Betamethasone effects in lymphoid organ

development and their leukocyte subsets were determined after birth. In vitro effects of

betamethasone were evaluated in splenocytes and dendritic cells in terms of viability,

phenotype and function. Additionally, the effect of betamethasone was assessed in islet

cells phenotype and function.

Betamethasone reduced T1D incidence in female offspring (22%) when compared to

sham group (75%). In treated mice, changes in the Vβ T cell repertoire pointed to a shift to

non-pathogenic T cells. In newborn mice, betamethasone caused thymus hypotrophy and

alterations in leukocytes subsets. Betamethasone caused in vitro toxicity to resting

lymphocytes and induced maturation-resistant dendritic cells, thus impairing autologous γδ

T lymphocyte proliferation and IL17 secretion. Finally, betamethasone was detrimental for

NIT-1 cells, arresting cell growth and reducing insulin secretion. Relevant transcriptome

changes were observed in a β-cell line and islets, as evidenced by differential expression

of genes related to autoimmunity, metabolism and islet mass

In conclusion, betamethasone modulates the developing immune system and influences

the susceptibility to experimental T1D, by direct effect to immune system cells and to

pancreatic β-cells.

Funding: ISCIII (PI15/00198), Deutsche Forschungsgemeinschaft (KFO296), AGAUR,

GenCat.

www.sci.cat 19

Oral Communications Session III From Innate to Adaptative Immunity 11 - 16

11 Comparing the efficiency of two clinical grade stimuli on

BDCA3+ mDCs by using transcriptomics for immunotherapy

Georgina Flórez Grau1; Til S. M. Mathan

1; Tom van Oorschot

1; Sonja I. Buschow

2; Gerty Schreibelt

1;

Inge Reinieren-Beeren1; David Sancho

3; Carlos Alfaro

4,5,6,7; Ignacio Melero

4,5,6,7; Carl G. Figdor

1;

Jolanda M. de Vries1,8

; Johannes Textor1

1Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen.;

2Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam.;

3Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.;

4Division of Gene

Therapy and Hepatology, Centre for Applied Medical Research (CIMA), Pamplona, Spain; 5Department of

Oncology, University Clinic of Navarra, Pamplona, Spain.; 6Department of Immunology, University Clinic of

Navarra, Pamplona, Spain.; 7CIBERONC, Madrid, Spain.;

8Department of Medical Oncology, Radboud

Institute for Molecular Life Sciences, Radboudumc, Nijmegen.

Maturation of dendritic cells (DCs) is considered critical in cancer immunotherapy. Among

the primary circulating blood DCs, there are two main subsets, the myeloid DCs (mDCs)

and the plasmacytoid DCs (pDCs). The mDC subset can be subdivided into CD1c+

(BDCA1) mDCs and CD141+-Clec9A+ (BDCA3+)mDCs. Each subset has been shown to

have specific functions. Whereas pDCs are known to produce high amounts of type I

interferons (IFNs) in response to viral infection and CD1c+ mDCs are able to sense

bacterial pathogens, BDCA3+ mDCs are highly efficient cross-presenters to CD8 T cells,

raising interest on them as target for DC-based vaccines.

Here, we evaluate two clinical grade stimuli for peripheral blood BDCA3+ mDCs a rare DC

subset that is currently being explored for use in immunotherapy. We applied an unbiased

transcriptome-based method using both RNA-sequencing (RNA-seq) and microarrays. In

particular, we analyzed the mRNA of human BDCA3+ mDCs upon activation with two

clinical-grade adjuvants: Hiltonol (poly IC, a TLR3 ligand) and protamine RNA (pRNA,

aTLR7/8 ligand), and compared the data to unstimulated counterparts.

Our results, showed that Hiltonol and pRNA lead to almost identical changes in BDCA3

mDCs, both at the transcriptome and at protein levels. In addition, the gene ontology (GO)

term analysis suggests that these changes were mainly related to activation and

maturation pathways, including induction of type I IFN and IL-12 transcription, while

pathways related to adverse effects or cell damage were not significantly affected. The

combination of both stimuli in the DC cultures gave a very similar result as compared to

either stimulus alone, suggesting no synergistic effect.

In conclusion, both Hiltonol as well as protamine mRNA are equally potent clinical grade

adjuvants with comparable effects on BDCA3 mDCs after short-term culture. This paves

the way for introducing BDCA3 mDCs into a clinical setting.

20 www.sci.cat

Oral Communications Session III From Innate to Adaptative Immunity 11 - 16

12 Gene Expression Profile of Tolerogenic Dendritic Cells

Differentiated with Vitamin D3, Dexamethasone and

Rapamycin

Juan Navarro-Barriuso1,2

; María José Mansilla1,2

; Bibiana Quirant-Sánchez1,2

; Aina Teniente-Serra1,2

;

Alex Sánchez-Pla3; Mar Naranjo-Gómez

1; Cristina Ramo-Tello

4; Eva M. Martínez-Cáceres

1,2

1Immunology Division, Germans Trias i Pujol University Hospital and Research Institute;

2Department of

Cellular Biology, Physiology and Immunology, Universitat Autonoma de Barcelona; 3Department of Statistics,

University of Barcelona; 4Multiple Sclerosis Unit, Department of Neurosciences, Germans Trias i Pujol

University Hospital.

Background: Tolerogenic dendritic cell (tolDC)-based therapies have become promising

approaches for the treatment of autoimmune diseases by their potential ability to restore

immune tolerance in an antigenspecific manner. There is a broad variety of protocols to

generate tolDC in vitro, being their differentiation in the presence of vitamin D3 (vitD3-

tolDC), dexamethasone (dexa-tolDC) or rapamycin (rapa-tolDC) three of the most

frequent. However, the characteristics of these cells are very heterogeneous, thus making

the need to find common genetic pathways and biomarkers of high relevance.

Objective: To compare the transcriptomic profile of vitD3-tolDC, dexa-tolDC and rapa-

tolDC in order to find common induced pathways and biomarkers.

Methods: Monocyte-derived dendritic cell differentiations of immature (iDC), mature

(mDC), vitD3-tolDC, dexa-tolDC and rapa-tolDC from 5 healthy donors were generated,

and a microarray analysis was performed (Affymetrix). Results were normalized and

filtered, and differentially expressed genes (DEG) were selected. A Gene Set Enrichment

Analysis (GSEA) was performed to select common enriched pathways. Statistical analyses

were performed using R software.

Results: Common DEG could not be found for the three tolDC, although 14 genes (many

of them immunerelated) appeared up-regulated in at least one condition. GSEA revealed

11 common protein sets differentially expressed in tolDC. However, all of them were

induced for vitD3-tolDC and dexa-tolDC, while down-regulated in rapa-tolDC.

Conclusions: The analysis revealed that, despite not sharing potential common

biomarkers, vitD3-tolDC and dexa-tolDC presented similar transcriptomic profiles,

suggesting an induction of immune tolerance through common pathways, while rapa-tolDC

seem to develop their function through different ones.

www.sci.cat 21

Oral Communications Session III

From Innate to Adaptative Immunity 11 - 16

13 Optimal response to dimethyl fumarate is mediated by a

reduction of th17.1 cells after 3 months of treatment.

María José Mansilla1,2

; Juan Navarro-Barriuso1,2

; Sílvia Presas-Rodríguez3,4

; Aina Teniente-Serra1,2

;

Bibiana Quirant-Sánchez1,2

; Irene Bragado Trigo3; Cristina Ramo-Tello

3,4; Eva Martínez-Cáceres

1,2

1Immunology Division, Germans Trias i Pujol University Hospital and Research Institut.,

2Department of

Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 3Multiple Sclerosis Unit,

Department of Neurosciences, Germans Trias i Pujol University Hospital, 4Department of Medicine,

Universitat Autònoma de Barcelona.

Aim: Dimethyl fumarate (DMF) is one of the most promising therapies for relapsing-

remitting multiple sclerosis (RRMS) patients since it exerts immunomodulatory and

neuroprotective effects. However, a percentage of RRMS patients do not exhibit an

optimal response to DMF. The objective of this study was to identify early biomarkers of

treatment response by analysing changes in peripheral leukocyte subpopulations directly

in whole blood samples.

Methods: Longitudinal and prospective study analysing peripheral blood leukocyte

subpopulations in 22 RRMS patients before initiating DMF treatment (baseline) and

following 1, 3, 6 and 12 months of followup. Patients were classified as NEDA (no

evidence of disease activity) or ODA (ongoing disease activity) based on clinical and

radiological data obtained during the follow-up, and differences between groups of patients

were analyzed.

Results: The beneficial effect of DMF was associated with a specific depletion of memory

CD4+ and CD8+ T lymphocytes and B cells. Importantly, only NEDA patients showed: i) a

shift from a pro- to an antiinflammatory profile, with an increase of Th2 cells and a

decrease of Th17.1 lymphocytes; ii) an induction of transitional B cells; and iii) an increase

of regulatory CD56bright NK cells.

Conclusion: The optimal response to DMF is mediated by a shift to anti-inflammatory and

immunoregulatory profile, showing Th17.1 lymphocytes as a potential early biomarker of

treatment response.

22 www.sci.cat



14 Anti-Ly9 (CD229) targeting depletes marginal zone B cell and

prevents salivary gland infiltration in a mouse model of

Sjögren's Syndrome

Joan Puñet-Ortiz1; Manuel Sáez Moya

1; Marta Cuenca

1; Adriana Lázaro

1; Pablo Engel

1

1Immunology Unit, Department of Biomedical Sciences, Medical School, University of Barcelona

Sjögren’s Syndrome (SjS) is one of the most common chronic autoimmune. It is

characterized by abnormal B-cell hyperproliferation as well as cell infiltration and epithelial

damage of exocrine glands. It can develop serious extraglandular affectations, such as

respiratory/hepatic dysfunction, and marginal zone B-cell lymphoma. Several biologicals

have been tested in SjS without significant clinical efficacy. Here we report the effects of

an agonistic antibody against Ly9 (CD229), which is a cell surface molecule that belongs

to the SLAM family of immunomodulatory receptors, using NODH2h4 female mice as a

model of SjS-like disease. Female mice were treated with anti-Ly9 antibody or isotype

control at week 24, when all mice present SS-related autoantibodies, salivary gland

infiltrates and marginal zone (MZ) B cell pool enlargement. Plasma was collected before

and after treatment, and quantified by ELISA and immunofluorescence. B and T

lymphocyte subsets from lymphoid tissues and salivary glands were analyzed by flow

cytometry and immunohistochemistry. Salivary glands were also studied in paraffin-

embedded sections. Autoantibody levels (anti-ANA, anti-Ro, anti-dsDNA and RF) were

decreased or impeded to increase over time after anti- Ly9 treatment. Moreover, this

treatment induced the depletion of key lymphocyte subsets involved in SS pathology such

as MZ and germinal center B cells in the spleen, draining lymph nodes and salivary

glands. Importantly, mice receiving anti-Ly9 mAb showed a reduction of the infiltrate within

salivary glands (isotype control: 0.61 mm2 versus anti-Ly9: 0.15 mm2). Finally, we tested

anti-Ly9 mAb in early stages before SjS onset and we observed that mice treated at week

12 with anti-Ly9 remained protected from of salivary gland cell infiltrates formation. These

data indicate that Ly9 is a promising potential therapeutic target for the treatment of SjS.

www.sci.cat 23



15 Decreased IFN-γ production in umbilical cord blood is

associated with Breg cells

Ana Esteve-Solé1,2

; Àngela Deyà-Martínez1,2

; Yiyi Luo1,2

; Irene Teixidó3; Alexandru Vlagea

2,4; Jordi

Yagüe2,4

; Ana María Plaza-Martín1,2

; Manel Juan2,4

; Laia Alsina1,2

1Clinical Immunology and PID Unit, Pediatric Allergy and Clinical Immunology Dep. HSJD. IRSJD. UB.;

2Clinical Immunology Unit Hospital Sant Joan de Déu-Hospital Clínic, Barcelona;

3Materno-fetal Department,

Hospital Clínic de Barcelona, Barcelona; 4Immunology service, Biomedic Diagnostic Center, Hospital Clínic

de Barcelona, UB, IDIBAPS, Barcelona.

Background and aims: Umbilical cord blood (UCB) is considered a safer source for stem

cell transplantation; however, infection is a major problem of this source of progenitors. We

have recently shown that Breg cells are increased in UCB and inhibit IFN-γ production by

T cells.

Methods: We have evaluated UCB response to live BCG: whole blood culture was

performed on UCB of healthy neonates (n=14) and healthy adult’s peripheral blood (n=13),

using cytokine production as a readout. Besides, Breg cell frequency

(CD19+CD24hiCD38hi) was evaluated by flow cytometry.

Results: We observed a diminished response to BCG challenge in neonates compared to

adults, with a decreased IL-6, IFN-γ and IP-10 stimulation ratio (SR) after mycobacterial

challenge (p=0.012 and p< 0.001 and p=0.002, respectively). IFN-γ (p<0.001, R:-0.76) and

IP-10 (p<0.001, R:-0.85) production after mycobacterial challenge inversely correlated with

Breg cell frequency in UCB.

Conclusions: We showed for the first time an association between Breg cell frequency

and antimycobacterial response in UCB, which might suggest that the benefit of Breg in

tolerogenicity may have a counterpoint: the reduced production of IFN-γ in response to

mycobacteria, leading to an increased susceptibility to these infections. Nonetheless, this

observation could be of special interest for transplantation in diseases with constitutively

increased IFN-γ production, such as in IFNGR1 deficiency.

This study was supported by the projects PI15/01094, PFIS0200 (AC16/00025) and

PI18/00223 to LA, integrated in the Plan Nacional de I+D+I and cofinanced by the ISCIII –

Subdirección General de Evaluación y Formento de la Investigación Sanitaria – and the

Fondo Europeo de Desarrollo Regional (FEDER), by “Subvencions per a la Intensificació

Facultatius Especialistes” del Departament de Salut de la Generalitat de Catalunya.

Programa PERIS 2016-2020 (Referencia: SLT006/17/00199)” and by a 2017 Leonardo

Grant for Researchers and Cultural Creators, BBVA Foundation to LA.

24 www.sci.cat



16 Low mucosal microbial load favors fecal microbiota

colonization and anti-inflammatory response

Guillaume Sarrabayrouse1; Stefania Landolfi

2; Marta Pozuelo

1; Encarna Varela

1; Allison Clark

1; David

Campos1; Claudia Herrera

1; Alba Santiago

1; Kathleen Machiels

3; Severine Vermeire

3; Marc Martí

4;

Eloy Espin4; Chaysavanh Manichanh

1

1Department of Gastroenterology, Vall d’Hebron Research Institute, Barcelona, Spain;

2Anatomical

Pathology Department, Vall d'Hebron University Hospital, Vall d'Hebron Research Institute; 3Department of

Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium; 4Unit of Colorectal Surgery,

Department of General and Digestive Surgery, Vall d'Hebron University Hospital.

Background and aims: Fecal microbiota transplantation (FMT) is much less efficient in

achieving the clinical remission of Crohn’s disease (CD) than the cure of Clostridium

difficile infection, thereby suggesting that the host immune system rejects the transplanted

microbiota. Our aim was to study the mechanism leading to mis-communication between

recipient intestinal mucosa and donor microbiota.

Methods: Using an explant tissue model, we examined changes in the mucosal

microbiome community, immune responses and tissue structure upon contact with a fecal

suspension obtained from a selected healthy donor (HD-FS). We analyzed explant tissues

from 28 patients (CD and controls) undergoing intestinal resection for the experimental

cohort and biopsies from 26 CD patients for the validation cohort.

Results: We showed that histological damage to the mucosal barrier was dependent on

the concentration of microorganisms present in the HD-FS. Cytokine release and tissue

damage were significantly greater in inflamed CD tissues compared to control and non-

inflamed CD tissues. Tissues harboring an initial low microbial load showed a shift in

composition towards that of the HD-FS, a significant increase in the relative count of

Faecalibacterium prausnitzii, and a higher anti-inflammatory immune response (P < .05)

compared to those with a high microbial load.

Conclusion: Our results indicate that the use of FMT for patients with active disease may

compromise its outcome. Furthermore, they support the stratification of FMT recipients on

the basis of tissue microbial load as a strategy to ensure successful colonization and anti-

inflammatory response.

www.sci.cat 25

e-poster List

Posters Clinical Immunology 1 - 19 The authors will attend the poster on 15/11/2018: 17:00h; 16/11/2018: 11:00h, 13:30h, 16:30h.

1 Combined therapy for type 1 diabetes based on drug-

repurposing. Immunotherapy and regenerative strategies.

Adrián Villalba Felipe1; Silvia Rodríguez-Fernández

1; David Perna-Barrull

1; Rosa Ampudia

1; Irma

Pujol-Autonell1; Clara Ehrenberg

1; Eva Aguilera

2; Mireia Coma

3; Daniel Maspoch

4,5; Federico

Vázquez2; Marta Vives-Pi

1,6

1Immunology Section, Germans Trias i Pujol Research Institute, UAB, Badalona, Spain,

2Endocrinology

Section, Germans Trias i Pujol University Hospital, Badalona, Spain, 3Anaxomics Biotech, Barcelona, Spain,

4Catalan Institute of Nanoscience and Nanotechnology, Bellaterra, Spain,

5ICREA, Barcelona, Spain,

6IBERDEM, ISCIII, Madrid, Spain

Type 1 diabetes mellitus (T1D) is a chronic metabolic disease caused by the autoimmune

destruction of insulin-producing β-cells. To cure T1D, the definitive arrest of β-cell

destruction must be accompanied by βcell regeneration. The aim of this study was to

develop a new combination therapy for T1D by coupling a previously-developed liposome-

based immunotherapy (PMID: 26039878) with β-cell regenerative compounds. To that

end, we used a systems biology approach, drug repurposing to determine new uses for

approved drugs. By using this technology, 21 approved-compounds that could putatively

promote β-cell regeneration were obtained. Three drugs (AVI1, AVI2 and AVI3, protected

by intellectual property rights) were selected based on predicted efficacy values. The

therapeutic effect of these drugs for β-cell regeneration was tested in immunodeficient

non-obese diabetic NOD-Scid IL2rg-/-mice (NSG) rendered diabetic by streptozotocin.

Based on the following results, AVI1 was the best candidate. Preliminary results

demonstrated that daily s.c. administration of AVI1 reversed hyperglycaemia of mice with

T1D. Intraperitoneal glucose tolerance test showed that diabetic NSG mice treated with

AVI1 recovered normoglycaemia at 210 min, whereas diabetic non-treated mice remained

hyperglycaemic. The effect of AVI1 in combination with liposome-based immunotherapy

was determined in the spontaneous model of autoimmune T1D, the NOD mouse.

Combination therapy reversed hyperglycaemia in diabetic NOD mice during the first two

weeks of treatment, more efficiently than in NOD mice only treated with immunotherapy.

The assessment of AVI1 in the incidence of autoimmune T1D in the NOD model revealed

no detrimental effect despite onset acceleration. AVI1 increases the number of budding

islets, shifting the insulitis to those when compared to mature islets. In summary, a

combined therapy consisting of a specific immunomodulatory strategy and a β-cell

regeneration agent holds a therapeutic potential in T1D by restoring tolerance and aiding

in b-cell mass recovery.

Funding: La Marató (201632_10); AGAUR, Gencat.

26 www.sci.cat

Posters

Clinical Immunology 1 - 19 The authors will attend the poster on 15/11/2018: 17:00h; 16/11/2018: 11:00h, 13:30h, 16:30h.

2 Detection of antibodies against neurofascin-155 in a patient

with chronic demyelinating inflammatory polyradiculoneuro-

pathy

Leticia Alserawan de Lamo1; M. Victoria Rubiales

1; M. Cinta Lleixà

2,3; M. Carmen Hernández-

Lafuente1; Elisabeth Moltó-Lacosta

1; Gemma Boera-Carnicero

1; Teresa Franco Leyva

1; Cándido

Juarez1; Luis Querol

2,3; Laura Martínez-Martínez

1

1Immunology Department, Hospital de la Santa Creu i Sant Pau,

2Neuromuscular Diseases Unit, Neurology

Department, Hospital de la Santa Creu i Sant Pau, 3Centro para la Investigación Biomédica en Red en

Enfermedades Raras, CIBERER.

Introduction: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a

heterogeneous autoimmune disease affecting peripheral nerves. Antibodies targeting

proteins at node of Ranvier such as contactin-1 (CNTN1), neurofascin-155 (NF155),

contactin-associated protein 1 (CASPR1), and nodal neurofascins, have been associated

with different CIDP subsets. In the case of anti-NF155, patients show predominantly distal

weakness, ataxia and low-frequency tremor. These patients do not usually respond to

intravenous immunoglobulin (IVIG) but respond well to B cell depleting therapies.

Clinical Case: We report a 56-year-old male who presented with an episode of

paresthesia in both hands in 2007. Afterwards, he also suffered from other two episodes

characterized by distal weakness, tremor and sensitivity affectation that caused transient

inability to walk. CIDP diagnosis was then established and treatment with IVIG,

corticosteroids and immunosuppressors was administered with no remarkable response.

In March 2018 the patient was referred to our hospital to complete the CIDP diagnosis.

Antibodies against nodal and paranodal proteins by immunocytochemistry on transfected

HEK cells, and paraneoplastic antibodies by indirect immunofluorescence on monkey

brain and cerebellum, were analyzed. HLA alleles were also studied. We found

autoantibodies against NF155 protein, and a characteristic pattern in the cytoplasm of

Purkinje cells. The patient presented the HLA-DRB1*15:01 allele, in accordance to the

strong association of antiNF155 positive CIDP patients with HLA-DRB1*15, recently

described by our group. All these findings led to the prescription of Rituximab and

plasmapheresis cycles which has resulted in a progressive clinical improvement.

Conclusions: The patient showed autoantibodies against NF155 that perfectly correlates

with the phenotype of antiNF155 positive CIDP subjects. The staining of Purkinje cells on

cerebellum may lead to immunologists to suspect the presence of autoantibodies against

NF155 in patients with CIDP diagnosis. These autoantibodies must be confirmed by

immunocytochemistry on transfected NF155-HEK cells.

www.sci.cat 27

Posters


3 Quantification of reactivity discrepancies between alleles of

the same HLA-class I serological group

Iñaki Ortiz de Landazuri1; Natalia Egri

1; Montse Digón

1; Alexandra Manchón

1; Eduard Palou

1; Jaume

Martorell1

1Servei Immunologia Hospital Clínic de Barcelona.

Background: HLA alloresponse for sensitized patients has historically been based on

serologically defined HLA specificities. Nowadays, single allele bead (SAB) technology

allows differentiation between alleles of the same serologic group but with different amino

acid sequences.

Objectives: To quantify reactivity discrepancies between different alleles belonging to the

same HLA-class I serological group, in a large kidney transplant candidates’ cohort.

Methods: Sera from patients on a kidney transplant waiting list (n=1000) were analyzed

for anti-HLA antibodies using solid phase screening. Patients with positive results in the

screening (n=350) were examined using SAB technology (KIT Lifecodes LSA Immucor®).

Each allele was considered positive if MFI>1500 and [MFI/LRA]>4. The frequencies of the

alleles in the local population were also annotated. Those patients with, at least, one

positive bead for every HLA-I (A, B, C) were studied, and reactivity patterns of all beads

representing the corresponding serologic group were quantified. We use here the term

uniform pattern when all the beads are positive and if not, no-uniform pattern.

Results: HLA-A*11, HLA-A*24, HLA-A*68, HLA-B*35, HLA-B*44, HLA-C*07 showed a

uniform pattern in ≥85% of the cases; while HLA-B*07 showed it in 75%. HLA-C*08, HLA-

C*04 presented a no-uniform pattern in >40% of the cases. (Tables with data are shown in

the attached document).

Conclusions: The uniform pattern of the studied serologic groups (HLA-A*11, HLA-A*24,

HLA-A*68, HLA-B*35, HLA-B*44, HLA-B*07, HLA-B*07, HLA-C*04, HLA-C*08) explained

a range between the 50% and 96% of the sensitized recipients for these serological

groups. A typing strategy defining at least the alleles studied in the used SAB panel would

benefit hypersensitized patients, recognizing frequent nonuniform allele patterns. This

approach should take in consideration allele frequencies in the studied populations.

28 www.sci.cat

Posters


4 A novel CTLA4 mutation in patient with a severe chronic

enteropathy

Teresa Franco Leyva1; Andrés Baucells de la Peña

1; Anna Yuste Estevanez

1; Leticia Soriano

1; Leticia

Alserawan de Lamo1; Rebeca Pérez de Diego

2; Laura Martínez-Martínez

1; Oscar de la Calle Martín

1

1Immunologia. Hospital de la Santa Creu i Sant Pau,

2Instituto de Investigación Hospital Universitario La

Paz.

Heterozygous germline mutations in cytotoxic T-lymphocyte antigen 4 (CTLA4) are

responsible for autosomal dominant immune dysregulation with immunodeficiency

syndrome. Patients can present multiple clinical manifestations, the most frequent being

hypogammaglobulinemia (84%), lymphoproliferation (73%), cytopenia (59%) and

respiratory (68%), gastrointestinal (59%) and skin involvement (56%) reminding

autoimmune and immunodeficiency symptoms.

We present a 41 year-old male born in Venezuela, who suffered from chronic diarrhea

since he was 15 years-old, accompanied by episodes of secondary weight loss, anemia

and severe hypokalemia. He was initially diagnosed as Celiac disease refractory to diet,

with partial response to corticoids. He moved to Spain 3 years ago. A detailed anamnesis

revealed parotid hypertrophy, skin lesions including abundant warts and condilloma

accuminata. It also showed a familiar background of hereditary ataxia in several close

members and gastric neoplasia in his grandmother. Immunological analysis showed

hypogammaglobulinemia, profound B lymphopenia and absence of anti-transglutaminase

antibodies. The intraepithelial lymphocyte pattern was not compatible with Celiac disease,

despite having a risk HLA association (HLA-DRB1*0301, DQA1*0501 and DQB1*0201).

The imaging and histological study revealed infiltrating inflammation, atrophy and

metaplasia in all digestive tissues.

BTK analysis discarded the diagnosis of Bruton disease. An extended study by NGS

confirmed by Sanger sequencing showed a heterozygous mutation in CTLA4 gene, not

previously described. The substitution of a G by a T (c.G308T) causes a missense

mutation changing a Cysteine by a Phenilalanine in the position 103 (p.C103F). A previous

but different missense mutation had been described in this same aminoacid: p.C103S.

Conclusions: CTLA4 mutations cause autosomal dominant immune dysregulation with

immunodeficiency syndrome resulting in a wide variety of symptoms. Our patient debuted

with chronic diarrhea with partial response to corticoids. He presented with

agammaglobulinemia and B lymphopenia. After ruling out Bruton disease, we found a

novel missense mutation p.C103F in CTLA4 gene.

www.sci.cat 29

Posters


5 Unraveling Vedolizumab mechanism of action in IBD

Marisol Veny1; Alba Garrido

1; Helena Bassolas

1; Maria Carme Masamunt

1; Miriam Esteller

1; Montse

Arroyes1; Ana Corraliza

1; Julià Panés

1; Azucena Salas

1

1Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain

Vedolizumab (VDZ) is approved for IBD therapy since 2014. VDZ targets the integrin

alpha4-beta7 (a4b7) which facilitates the migration of leukocytes to the intestine.

Remission with VDZ is achieved in <45% of patients in the case of ulcerative colitis (UC).

This lack of universal efficacy and the current diversity of drugs for IBD justify the

necessity of biomarkers to help in the election of the proper drug for each specific patient.

In this regard, our objective is to study the mechanism of action of VDZ by assessing its

effect in UC patients. Our specific objectives are: 1) analyze the frequencies of leukocytes

in the intestine and peripheral blood; 2) characterize the expression of integrins a4b7,

a4b1 and aEb7 in lymphocytes and 3) determine the a4b7 occupancy achieved by VDZ.

Our flow data show that percentages of T and B cells in the intestine decrease at week 14

and 46 after treatment initiation. This observation is specific to VDZ treatment since anti-

TNF treated patients do not show this reduced recruitment of lymphocytes. Moreover, VDZ

therapy reduces the amount of a4b7 and a4b1 present in the membrane of most

lymphocytic populations in blood and intestine. Finally, we show that a4b7 occupancy is

total in all patients, time points and immune populations studied. In conclusion, our results

confirm that the current regime of VDZ blocks the migration of T and B cells to the

intestinal lamina propria. This effect is due to the complete blockade of a4b7 but probably

helped by the reduced presence of the integrin in the cell surface. The final aim of this

ongoing project is to correlate response/remission to VDZ to one of the studied parameters

establishing a good biomarker for this drug in UC patients

jlloberas

CANCELED

jlloberas

CANCELED

30 www.sci.cat

Posters


6 Development of an ELISPOT assay to determine and quantify

specific anti-dsDNA antibody secreting cells. A novel

biomarker in Systemic Lupus Erythematosus?

Albert Pérez-Isidro1,3

; Arturo Llobell1,3

; Marina Caicedo1,3

; Ana Esteve-Solé4,5

; E Azucena González-

Navarro1,3

; Laura Rubio1,3

; Sergi Prieto2,3

; Gerard Espinosa2,3

; Mila García2,3

; Estíbaliz Ruiz-Ortiz1,3

;

Odette Viñas1,3

1Servei d'Immunologia, Centre de Diagnòstic Biomèdic (CDB),

2Servei de Malalties Autoimmunes (ICMD) de

l'Hospital Clínic de Barcelona, 3Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona,

4Clinical

Immunology Unit Hospital Sant Joan de Déu-Hospital Clínic, Barcelona, Spain, 5Clinical Immunology and

Primary Immunodeficiencies Unit, Institut de Recerca Sant Joan de Déu.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune and inflammatory disease

driven by autoantibodies and characterized by recurrent disease flares. Antibodies against

double-stranded DNA (dsDNA-Ab) are widely used to diagnose SLE. To evaluate the

disease activity (DAct) in patients, complement values and dsDNA-Ab titres in serum are

the main tools. Published data suggest that the detection and quantification of peripheral

blood circulating anti-dsDNA antibody-secreting cells (PBdsDNA-ASC) may be a

promising biomarker for DAct, Renal Involvement (RInv) and flare risk in comparison to

serum complement and anti-dsDNA-Ab in SLE patients.

Therefore, the main aim of this study was to optimize and to standardize an ELISPOT

assay (establishing a cut-off value) able to determine and quantify PB-dsDNA-ASC. A

secondary objective was to check for a positive correlation of ELISPOT results with DAct,

RInv and short-term flare prediction.

Seventy-nine individuals distributed in 4 groups (29 SLE patients, 12 SLE-Overlap

patients, 20 Disease controls and 18 Healthy individuals) were included. PB-dsDNA-ASC

were analysed using ELISPOT and complement (C3, C4 and CH50) serum levels and

anti-dsDNA-Ab titres were measured by chemiluminecence (CL) and indirect

immunofluorescence (IIF) methods.

The assay conditions for PB-dsDNA-ASC ELISPOT were set-up, and the cut-off value for

a positive ELISPOT result was established at >7,45 spots. Sensitivity and specificity were

of 57,9% and 86%, respectively. In our cohort PB-dsDNA-ASC ELISPOT results seem to

better classify patients with DAct and RInv and for short-term flare risk.

Thus, PB-dsDNA-ASC ELISPOT, seem to be a better biomarker for DAct and RInv, and

for a short-term flare risk than usual follow-up methods. However, a larger number of

samples, a better homogeneity between studies, a longer own patients’ follow-up and a

better understanding of medication dosage effects are needed to confirm that we are in

front of a potential novel and more accurate biomarker for SLE patients.

www.sci.cat 31

Posters


7 Clinical profile characterization of myositis-associated

autoantibodies in our cohort of patients with autoinflammatory

myopathies

Clara Esteve Cols1,2

; Jordi Camins Fàbregas3; Àlex Soriano Martínez

1; Maria Martínez González

1;

Susana Holgado Pérez3; Eva Mª Martínez-Cáceres

1,2; Bibiana Quirant-Sánchez

1,2

1Immunology Department Hospital Germans Trias i Pujol, Badalona, Spain,


Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, 3Reumathology Department

Hospital Universitari Germans Trias I Pujol, Badalona, Spain.

Background: Autoinflammatory myopathies are a heterogeneous group of autoimmune

diseases. They are expressed with muscle weakness and multisystemic involvement with

disability, distinct cutaneous rashes, ulceration, calcinosis, malignancy and interstitial lung

disease (ILD). Dermatomyositis (DM), polimyositis (PM), necrotizing myopathy and

juvenile myositis are the most frequent pathologies. The diagnosis includes a range of

diagnostic tests such as electromyography, muscle and/or skin biopsy and muscle

enzymes. In addition, autoantibodies that target both nuclear and cytoplasmic components

of the cell have been identified in over 50% of patients. In recent years, new specificities

related to DM have been described such as NXP-2 (Nuclear matrix protein 2), SAE 1/2

(Anti-small ubiquitin-like modifier activating enzyme), MDA-5 (melanoma-differentiation

associated gene 5) and TIFɤ (transcriptional intermediary factor 1-gamma).

Objectives: The aim of this study is to describe the frequency and the clinical phenotype

of different myositis-associated autoantibodies (MAAs).

Methodology: A retrospective study with 35 patients from Hospital Germans Trias i Pujol

diagnosed of some autoinflammatory myopathies was performed and the prevalence and

clinical profile of the MAAs analyzed.

Results: Twenty-three patients were positive for one of the MAAs representing a

frequency of 65.71%. SAE was the most prevalent specificity, and its clinical profile was

characterized by an amyopathic dermatomyositis at onset, evolving to the development of

myositis with highly elevated creatine-cinase (CK) enzyme levels. Jo1 was the most

frequent aminoacyl-tRNA synthetase with a clinical phenotype characterized by myositis

and ILD. MDA-5 clinical profile was characterized by an amyopathic dermatomyositis with

severe cutaneous manifestations at onset. One MDA-5 positive patient developed ILD.

The other MAAs were less prevalent.

Conclusions: MAAs have an increasing utility as both diagnostic and prognostic

biomarkers. The presence of one of these new specificities can help in the classification of

myositis patients predicting further disease complications and possible treatment

responses.

32 www.sci.cat

Posters


8 Positive serum anti-phospholipase A2 receptor antibodies may

avoid renal biopsy in patients with primary membranous

nephropathy

Bibiana Quirant-Sánchez1,2

; Clara Esteve Cols1,2

; Maruja Isabel Navarro Díaz3; Àlex Soriano Martínez

1;

Maria Martínez Gonzàlez1; Dolores López

4; Eva Mª Martínez-Cáceres

1,2

1Immunology Department, Laboratori Clínic Metropolitana Nord, Hospital Germans Trias i Pujol,

2Department

of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 3Nephrology Department

Hospital Universitari Germans Trias i Pujol, 4Pathological Anatomy Department Hospital Universitari

Germans Trias i Pujol.

Background: Membranous nephropathy (MN) represents a glomerular disease which is

the leading cause of nephrotic syndrome in adults. Two major autoantibodies, IgG4 anti-

phospholipase A2 receptor (PLA2R-Ab) and IgG4 thrombospondin type-1 domain-

containing 7A (THSD7A-Ab), have been related to the pathogenesis of primary MN (pMN).

Objective: We aim to analyse the relationship between the presence of anti-PLA2R-Ab

and anti-THSD7A-Ab in serum as well as PLA2R and IgG4 deposits in renal biopsy, and

define an algorithm for their use in the clinical practice.

Methodology: A total of 46 patients with biopsy-proven MN were included, primary

(pMN=38) and secondary (sMN=8). Serum PLA2R-Ab and THSD7A-Ab were detected by

cell-based indirect immunofluorescence assay and PLA2R-Abs were quantified by ELISA.

Renal PLA2R-Ab and IgG4 deposits were analysed by immunohistochemistry (n=37).

Results: Among the total of MN patients, 74 % had PLA2R deposits in renal biopsy.

Serum PLA2R-Ab was positive in 19 patients, n=18 (47%) pMN and n=1 (12,5%) sMN.All

of them were positive for renal PLA2R deposits in the biopsy. Only one patient was found

positive for serum THSD7A-Ab and renal IgG4 deposits, testing negative for renal PLA2R-

Ab deposits and serum PLA2R-Ab.

Conclusions: Given that all the patients with a positive PLA2R-Ab serology showed

PLA2R deposits when biopsied, we propose to start the study by analysing PLA2R-Ab

serum levels and if they are positive, avoid the biopsy. Only those patients with a negative

PLA2R-Ab serology would be required to undergo the analysis of PLA2R and IgG4

deposits through renal biopsy. From the last group, those patients negative for PLA2R

deposits but positive for IgG4 may undergo serum testing for THSD7A-Ab.

www.sci.cat 33

Posters


9 Th1Th17CM lymphocytes as predictive biomarker of disease

activity in RRMS patients under dimethyl fumarate or

fingolimod treatment

B. Quirant-Sánchez1,3

; S. Presas-Rodríguez2; M.J Mansilla

1,3; A.Teniente-Serra

1,3; J.V. Hervás-García

2;

L. Brieva4; E. Moral-Torres

5; A. Cano

6; E. Munteis

7; J. Navarro-Barriuso

1,3; C. Ramo-Tello

2; E.M.

Martínez-Cáceres1,3

1Immunology Division,Laboratori Clínic Metropolitana Nord,Hospital Universitari Germans Trias i Pujol,

2Multiple Sclerosis Unit, Department of Neurosciences,Hospital Universitari Germans Trias i Pujol,

3Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona,

4Neurology Department of Hospital Arnau Vilanova,

5Neurology Department of Hospital San Joan Despi

Moises Broggi, 6Neurology Department of Hospital de Mataró.,

7Neurology Department of Hospital del Mar,

Barcelona, Spain.

Introduction: Peripheral blood biomarkers to predictive disease activity in multiple sclerosis (MS)

patients have not yet been identified. Dimethyl fumarate (DMF) and fingolimod are oral treatments

for relapsing remitting MS (RRMS) patients that reduce clinical and radiological activity. DMF

induces a decrease in effector and central memory T cells while fingolimod blocks the egress of

lymphocytes from the lymph nodes, reducing the infiltration of autoreactive lymphocytes into the

central nervous system.

Objective: To identify potential whole blood biomarkers able to predict disease activity in MS

patients during treatment independent of their mechanism of action.

Methodology: We analyzed the immune phenotype of T lymphocyte subpopulations in peripheral

blood samples from 66 RRMS patients under DMF or fingolimod treatment by flow cytometry. A

correlation study between the percentage and absolute cell number of each lymphocyte

subpopulation with the presence of relapses or new MRI lesions during 12-month follow-up was

performed.

Results: From the 66 patients analyzed, 21 patients (33 %) underwent one or more relapses

during the follow-up. Patients who had undergone relapses showed higher percentage of Th1CM

cells (relapsed: 11.60 ± 4.17 % vs non-relapsed: 9.25 ± 3.17 %, p < 0.05) and Th1Th17CM cells

(relapsed: 15.65 ±6.15 % vs non-relapsed: 10.14 ± 4.05 %, p < 0.01) before initiating DMF or

fingolimod treatment (baseline). Kaplan-Meier analysis revealed that patients with Th1Th17CM

(CD4+ CCR7+ CD45RA-CCR6+ CXCR3+) cells >11.48% had a 50% relapse-free survival compared

to patients with Th1Th17CM cells <11.48% whose relapse-free survival was 88% (p=0.013, log-

rank test). Additionally, a high percentage of Th1Th17CM cells was also found in patients with MRI

activity (No MRI activity: 9.82 ± 4.06% vs MRI activity: 14.02 ± 5.87 %, p < 0.01).

Conclusions: We have identified Th1Th17CM cells as a lymphocyte subpopulation increased at

baseline in peripheral blood of patients with a higher risk to develop relapses or new MRI lesions

during the first year of treatment with DMF or fingolimod.

34 www.sci.cat

Posters


10 Effect of omalizumab in peripheral T cell subpopulations in

chronic urticaria

Cristina Alejandra López Rodríguez1; Nathalie Depreux

3; Armando Ruíz

1; Isabel Bielsa

2; Bibiana

Quirant-Sánchez 1; E.M. Martínez-Cáceres

1; Aina Teniente-Serra

1

1Servicio de Inmunología. Hospital Universitario Germans Trias I Pujol, Badalona,

2Servicio de

Dermatología. Hospital Universitario Germans Trias I Pujol, Badalona, 3Servicio de Alergología. Hospital

Universitario Germans Trias I Pujol, Badalona.

Introduction: Chronic urticaria (CU) is an spontaneous urticaria that lasts for at least 6

weeks without an allergic trigger. In 40% of the patients an autoimmune pathogenesis, IgE

-mediated, is involved. Severity and prognosis are highly variable among patients, and

therapeutic management needs to be personalized. Omalizumab, a IgG1κ monoclonal

antibody that binds free human immunoglobulin E (IgE) has shown therapeutic effect in

some patients.

Objective:To analyse the effect of omalizumab in peripheral blood T -cell subpopulations

of CU patients.

Materials and Methods:Naïve, central memory, effector memory, effector (Th1, Th2,

Th17)T-cell subpopulations and activation markers (CD38, HLA.DR) were analyzed in

peripheral blood (PB) of 49 CU patients (Omalizumab treatment (n=22); non-

immunomodulatory drugs (n=27)) and 50 healthy donors (HD).

Results: Compared to HD, CU patients in treatment with non-immunomodulatory drugs

showed lower percentages of CD4+DR+CD38+ [0,8(0,7-1)vs1,23(1,01-1,54), p<0,0001]

and CD4+DR+CD38[1,1(0,8-1,4)vs3,07(2,5-4,7), p<0.0001]. Percentages of CD8+DR-

CD38+ [21±3vs8±0,5%, p<0.0001] and CD4+ naïve [55±3vs41±2, p<0.0001]

subpopulations were increased. CU patients in treatment with Omalizumab, showed lower

percentage of CD4+HLA-DR+CD38+ [0,75(0,6-1,1) vs 1,23(1,01-1,54)%, p<0.0001],

CD4+DR+CD38-[1,7(0,7-3,15) vs 3,07(2,5-4,7)%,p=0,0006] and higher percentage of

CD8+DR-CD38+ [14±2 vs 8±0,5%,p=0,0001] and Th1 Central-Memory cells [12±0,8 vs

9±0,4%, p<0.0001] than HD. Patients under Omalizumab showed a decrease in CD4+

naïve [42±3 vs 55±3%;p=0.001]] and CD4+DRCD38+ [36±3vs52±3, p=0.0002] compared

to patients under non-immunomodulatory drugs. Th1CM [12±1vs9±1, p=0.013], Effector

Memory [5,7(4,6-10,2)vs4,2 (3,6-6,8))%, p=0.033] and Th2CM [8,5 (6,7-12,3)vs6,4(4,3-

8))%, p=0.019] cells were increased in Omalizumab patients.

Conclusions: Omalizumab induces changes in peripheral blood T-cell subpopulations of

CU treated patients, promoting a decrease of activated T subsets, and an increase of

effector Th1 and Th2 cells. The impact of these changes on treatment response deserves

further investigation.

www.sci.cat 35

Posters


11 Development of a national third-party specific T lymphocyte

bank for immediate use in infectious diseases after

transplantation.

Maria López-Montañes1,2

; Marta Grau-Vorster1,2

; Pere Barba3; Jesús Maroto

1; Cristina Moya

1; Sílvia

Sauleda1; Sergi Querol

1,2; Francesc Rudilla

1,2

1Banc de Sang i Teixits,

2Vall d’Hebron Research Institut,

3Hospital Universitari Vall d’Hebron.

Viral infections, mainly cytomegalovirus (CMV), Epstein-Barr (EBV), Adenovirus (ADV)

and BK virus are one of the main causes of morbidity and mortality after hematopoietic

stem cell transplantation or solid organ transplantation. According to previous studies, the

infusion of virus-specific T-lymphocytes (VSTs) can control both viral reactivation and de

novo infection resistant to available antiviral drugs. Nevertheless, sometimes it is difficult,

costly and time-consuming to find a seropositive and compatible donor.

The development of a national third-party VST bank from voluntary donors would allow

infusing safely and effective ready to use-HLA-matched VSTs at a reasonable cost.

The first step is the creation of a registry of donors stratified by HLA-compatibility with

most of the target population and reactivity against CMV, EBV, ADV and BK virus tested

by ELISPOT assay. Also, phenotypic and functional tests will be considered.

Frequent blood donors were identified and selected as possible candidates to be part of

the register. The criteria followed for the donor inclusion were: age under 55 years,

availability of high resolution HLA typing and not being excluded for hemodonation

according to Blood and Tissue Bank criteria.

Currently, blood from 137 donors has been collected, processed and the PBMCs have

been cryopreserved. Additionally, a robust VST expansion protocol has been developed.

Therefore, this registry will be used as a database of donors that can be called to obtain

blood or lymphoapheresis for direct selection of IFNγ+ cells or togenerate VST cell lines to

create the first Spanish third-party VSTs bank.

36 www.sci.cat

Posters


12 Anti-glomerular basement membrane antibodies in an HIV-

infected patient

Sergio Navarro Velázquez1; Francisco Morandeira Rego

1; Joan Torras Ambros

2; Monsterrat Goma

Gallego3; Elisabet Poyatos Cantón

1; Virginia Mas Bosch

1; Jordi Bas Minguet

1

1Immunology Department. Hospital Universitari de Bellvitge,

2Nephrology Department. Hospital Universitari

de Bellvitge, 3Department of Pathology. Hospital Universitari de Bellvitge.

Anti-glomerular basement membrane antibodies (anti-GBM) are very specific markers for

Goodpasture syndrome (GPS), characterized by glomerulonephritis and alveolar

hemorrhage and for rapidly progressive glomerulonephritis, which shows no pulmonary

hemorrhage. In these pathologies, the target autoantigen is collagen (IV) alpha-3 domain,

which is expressed both in the glomerular basement membrane and in the alveolar

membrane. These antibodies can be detected in the patient’s serum or as linear deposits

of IgG in the basement membrane and are involved in a type II hypersensitivity reaction.

We report a case of a 18-year-old boy, who presented to the emergency department after

4 months of malaise, astenia, anorexia, intermittent fever and a weight loss of 20 Kg.

General lymphadenopathy was detected during physical examination. Blood and urine

tests showed anemia, high creatinine level, decrease of glomerular filtration rate,

hematuria and proteinuria. Immunology tests revealed polyclonal

hypergammaglobulinemia, low-titres positive antinuclear antibodies (cytoplasmic pattern at

1:80) and positive anti-GBM antibodies: (177 CU; reference <20 CU) as the most relevant

finding. Anti-dsDNA, anti-ENA, anti-MPO and anti-PR3 tested negative. Finally, flow

cytometry test showed low CD4+ T cell count (209x106 cells/mL) and the patient tested

positive for HIV.

Given these lab findings, renal biopsy was performed showing HIV-Associated

Nephropathy without the hallmark of anti-GBM disease: linear deposits of IgG on the

glomerular capillary walls.

The anti-GBM antibodies found in this patient do not seem to be related to the clinical

manifestations. They presumably constitute non-pathogenic low affinity antibodies

produced as a result of B lymphocyte polyclonal activation in the context of HIV infection.

This case shows the importance of an accurate interpretation of positive anti-GBM

antibodies in HIV patients, as well as the need to perform a renal biopsy to confirm the

results before starting immunosuppression.

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Posters


13 Comparative study of two different HEp-2 slides for ANA

analysis

Sergio Navarro Velázquez1; Francisco Morandeira Rego

1; María Jesus García Giménez

1; Virginia Mas

Bosch1; Jordi Bas Minguet

1

1Immunology Department. Hospital Universitari de Bellvitge.

Introduction: Antinuclear antibodies (ANAs) are autoantibodies that are specific for cell

nucleus antigens, although they also include antibodies specific for cytoplasmic antigens.

Its determination in serum by indirect immunofluorescence on HEp-2 slides is considered

the most useful screening technique for systemic autoimmune diseases diagnosis and is

the most widely used. Different fluorescence patterns can be observed depending on the

manufacturer.

Objective: To compare HEp-2 slides for ANAs analysis from different manufacturers

(Inova and Aesku).

Methods: 159 patients' sera were analyzed in parallel with slides at a dilution of 1:40

following the manufacturers' instructions. All the preparations were independently

evaluated by two expert observers.

Results: There were no discrepancies between the two observers in terms of the patterns

observed. The following discrepancies were obtained between the 2 manufacturers:

•Aesku slides had more cells in metaphase.

1. Seven samples (4%) were positive for Aesku and negative for Inova, whereas seven

(4%) were negative for Aesku and positive for Inova.

2. Four samples (2%) gave a mitochondrial pattern with Aesku that was not observed with

Inova, whereas two samples (1%) were negative for Aesku and positive for Inova.

3. Three samples (2%) gave a rods and rings pattern with Inova not observed with Aesku.

4. Six samples (4%) gave discordant patterns between Aesku and Inova, of which:

a. Two samples with homogeneous pattern with Aesku were multiple nuclear dots and

fine speckled, respectively with Inova.

b. One sample with homogeneous nucleolar pattern with Aesku was speckled with

Inova.

c. Three samples with double pattern with Aesku were a simple pattern with Inova.

Conclusions:

The agreement between the two manufacturers is quite acceptable.

The mitochondrial pattern is the one with the most discrepancies.

The homogenous and homogeneous nucleolar pattern is observed more often with

Aesku.

The rods and rings pattern is not detectable with Aesku.

38 www.sci.cat

Posters


14 Effect of long-term treatment with anti-proinflammatory

cytokines in T cell subsets of psoriatic patients

Joan Climent1,2

; Jaime Notario5; Francisco Morandeira

1; Virginia Mas

1; Nuria Padullés

3; Montserrat

Coll3; Jordi Bas

1

1Hospital Universitari de Bellvitge. Immunology Department,

2Hospital Universitari Germans Trias i Pujol.

Immunology Department, 3Hospital Unversitari de Bellvitge. Pharmacy Department,

4Universitat de

Barcelona. Division of Immunology, 5Hospital Universitari de Bellvitge. Dermatology Department.

Introduction: Psoriasis is a chronic inflammatory T cell mediated skin disease. The

advance in the knowledge of its pathogenic mechanisms has allowed the development of

specific treatments blocking proinflammatory cytokines. These treatments are not exempt

of adverse effects such as infections or malignancies, although these events are present in

a low percentage.

Objective: To analyze the influence of long-term treatment with anti-TNF-ɑ or anti-IL23

monoclonal antibodies on peripheral blood T lymphocytes of psoriatic patients.

Material and Methods: A total of 39 psoriatic patients under long-term treatment with anti-

TNF-ɑ (N= 19, 6.05 ± 2.76 years of treatment) or with anti-IL-23 (N= 20, 4.15 ± 2.18 years

of treatment) were included. As a control group, 21 subjects with no autoimmune diseases

were included. The T cell subpopulations analyzed are specified in table 1. Additionally,

basic biochemistry, blood count, CRP (C-Reactive Protein), ESR (Erythrocyte

Sedimentation Rate), antinuclear antibodies and the clinical index PASI (Psoriasis Area

Severity Index) were also studied.

Results: A significant increase in absolute counts of central memory T CD4 (T CD4 CM)

cells and their subpopulations: Th1 CM, Th1/Th17 CM and Th17 CM lymphocytes were

detected in the anti-TNF-ɑ treated group. In the group treated with anti-IL23, only an

increase of absolute counts of T CD8 CM lymphocytes was found compared to the control

group. No differences were observed in the biochemical parameters, CRP, ESR, or

antinuclear antibodies between groups. All patients were in clinical remission status with

PASI≤ 3. No history of recurrent infections or malignancy in treated patients was reported.

Conclusions: Long-term treatment with anti-TNF-ɑ or anti-IL23 affects T cell

subpopulations in peripheral blood of the psoriatic patients. The differences observed in

our cohort, do not translate into an increase in the risk of infection or malignancy

compared to the general population.

www.sci.cat 39

Posters


15 Age-specific pediatric reference values for immunoglobulins,

complement proteins and extended lymphocyte subsets for

the diagnosis of primary immunodeficiencies

Marina García-Prat1,2,3

; Gemma Vila-Pijoan2,3

; Daniel Àlvarez-Sierra3; Susana Martos Gutierrez

2,3;

Guadalupe Gala Yerga2,3

; Esther García Guantes2,3

; Aina Aguiló-Cucurull2,3

; Sandra Salgado-

Perandrés2,3

; Sara Briongos-Sebastian2,3


; Roger Colobran2,3,4

; Isabel

Montserrat5; Andrea Martín-Nalda

1,2; Manuel Hernández-González

2,3; Ricardo Pujol-Borrell

2,3; Pere

Soler-Palacín1,2


1Pediatric infectious diseases and immunodeficiencies unit, Hospital Universitari Vall d'Hebron,

2Jeffrey

Model Foundation excellence center, Barcelona, Spain, 3Immunology division, Institut de Recerca Vall

d'Hebron, Universitat Autònoma de Barcelona (UAB), 4Department of cell biology, physiology and

immunology, Universitat Autònoma de Barcelona (UAB), 5Hematology division, Hospital Universitari Vall

d'Hebron (HUVH).

Background: For the accurate diagnosis of immunodeficiencies is crucial to compare patients'

immunology laboratory values with age-sex matched controls, yet there is a paucity of normal

values for most populations.

Objectives: To define appropriate reference values of extended lymphocyte subpopulations, T-cell

receptor excision circle (TRECs) levels and immunoglobulin levels, subclasses and complement

proteins in healthy pediatric donors between 1 month and 18 years of age.

Methods: We have generated pediatric reference ranges for IgG, IgA, IgM, IgD, IgG and IgA

subclasses, and C3 and C4 using the Optilite™ turbidimetric analyzer. Extended

immunophenotyping values were obtained by analysis of multiparameter flow cytometry panels for

T-cell subsets, B-cell subsets, Dendritic Cells, Monocytes and Natural Killer cells.

Results: The concentrations of IgG, IgA, and IgD showed an increase with age, while IgM

remained stable between groups. For IgG subclasses, no significant differences were observed in

IgG1 or IgG3, while IgG2 and IgG4 concentrations increased steadily with age. For both IgA1 and

IgA2, concentrations increased significantly with age. The concentration of C3 and C4 remained

stable across the groups, with no significant differences observed. Naive CD4+ and CD8+ T-cell

populations tended to decrease with age, with significant difference between groups, in parallel

with the reduction in thymic function assessed by TREC counts and the recent thymic emigrant

population. Relative numbers of Th cell populations tended to increase with age. The percentage

of class-switched B cell populations showed a significant increase between the youngest group

and the others.

Conclusion: This study provides essential data for interpreting immunoprotein levels and

extended immunophenotyping profiles in the pediatric and young adult populations, which could be

of value for the diagnosis of PIDs and immune-mediated diseases, particularly those associated

with subtle immunological abnormalities.

40 www.sci.cat

Posters


16 MicroRNA Expression Profiling Identifies miR-31 and miR-485-

3p as Regulators in the Pathogenesis of Discoid Cutaneous

Lupus

Cristina Solé Marcé1; Sandra Domingo Bover

1; Berta Ferrer

2; Teresa Moliné

2; Josep Ordi-Ros

1;

Josefina Cortés-Hernández1

1Department of Medicine, Systemic Diseases Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain,

2Department of Pathology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.

Cutaneous Lupus Erythematosus (CLE) involves several autoimmune dermatological

disorders and it can be considered an individual disease or as a manifestation of SLE

(Systemic Lupus Erythematosus). Subacute Cutaneous Lupus Erythematosus (SCLE) and

Discoid Lupus Erythematosus (DLE) are the most CLE prevalent forms. Despite sharing

histological similarities, clinically they differ in their course and prognosis suggesting

different pathogenesis: SCLE is characterized by epidermal lesions that cure after the

treatment whereas DLE presents skin lesions that evolve in to fibrotic areas and scarring

after being treated. Here, we show that DLE-affected skin has a specific microRNA

expression profile when compared with SCLE. Among the DLE-specific microRNAs, we

identified one keratinocyte-derived microRNA, miR-31, and one leukocyte-derived

microRNA, miR-485-3p. UV and TGF-β1 stimulation up-regulates miR-31 expression in

DLE. Specific miR-31 overexpression induces keratinocyte apoptosis and NF-κB pathway

activation with the production of related inflammatory cytokines and contributes to the

recruitment of neutrophils and intermediate monocytes at the inflammation site. IL-1α and

TGF-β1 stimulation increases the expression of miR-485-3p in peripheral mononuclear

blood cells (PBMCs) from DLE patients and induces T-cell activation, mainly of CD8

lymphocytes. In addition, miR-485-3p overexpression in dermal fibroblasts contributes to

fibrosis by targeting peroxisome PGC-1α. Collectively, our findings suggest that the

overexpression of miR-31 and miR-485-3p contributes to skin inflammation by regulating

the production of inflammatory mediators and attracting neutrophils and intermediate

monocytes in DLE lesions

www.sci.cat 41

Posters


17 HLA-B locus mismatches number and risk of IgA nephropathy

recurrence after Renal Transplantation

Natalia Egri1; Lida M. Rodas

2; Laura Rubio

1; María Dolores Fernández

1; Odette Viñas Gomis

1; Fritz

Diekmann2; Eduard Palou

1; Luis F. Quintana

2; Estibaliz Ruiz-Ortiz

1

1Department of Immunology, Hospital Clínic i Provincial de Barcelona, Spain,

2Department of Nephrology

and Renal Transplantation, Hospital Clínic i Provincial de Barcelona, Spain.

Background: IgA nephropathy (IgAN) represents the most common type of chronic

glomerulonephritis in the world. Glomerulonephritis recurrence is the third most frequent

cause of allograft loss at 10 years. It is widely suggested that genetic factors play a role in

the recurrence of IgAN. However, the identity of these genetic factors remains uncertain.

Objectives: The aim of this study was to evaluate the relationship between HLA class I

and II mismatches and the risk of recurrence of IgAN after a renal transplantation.

Methods: 82 kidney transplant recipients with IgAN (with or without biopsy proven

recurrence; 19 vs 63) and their donors were included. HLA Typing was available in all

individuals. Sequence-specific oligonucleotide polymerase chain reaction (PCR-SSO)

(Lifecodes, Immucor) and/or sequence-specific primer (PCR-SSP) (ALLSet + Gold SSP;

Invitrogen) techniques were used for typing HLA-A, -B and -DRB1 alleles. Analysis

between donor and receptor for HLA match/mismatch for each locus were studied.

Results: We studied HLA matching between 82 kidney transplant recipients with IgAN and

their renal donors. For each pair, the compatibility for HLA class I (A, B) and HLA class II

(DRB1) loci was analyzed stratifying them in 0, 1 and 2 mismatches. In the non-recurrence

group, 24/63 (38%) patients present 2 incompatibilities in HLA-A, 28/63 (44%) in HLA-B

and 15/63 (24%) in HLA-DRB1. On the other hand, in the recurrence group 3/19 (16%)

patients present 2 incompatibilities in HLA-A, 2/19 (11%) in HLA-B and 3/19 (16%) in HLA-

DRB1.

Conclusion: In kidney recipients a greater HLA mismatch is related to a less recurrence of

the disease (IgAN), reaching statistical significance for HLA-B locus. Based on these

results, it may be advisable to select a non HLA identical donor for renal transplantation in

these patients.

42 www.sci.cat

Posters


18 Resolving KIR and HLA genotypes simultaneously using Next-

Generation Sequencing

Laia Closa1,2

; Francisco Vidal2,3

; Maria J. Herrero1; Jose L. Caro

1,2

1Histocompatibility and Immunogenetics Laboratory, Blood and Tissue Bank, Barcelona, Spain,

2Transfusional Medicine Group, Vall d’Hebron Research Institute, Barcelona, Spain,

3Congenital

Coagulopathy Laboratory, Blood and Tissue Bank, Barcelona, Spain.

Killer cell immunoglobulin-like receptors (KIR), considered the most polymorphic natural

killer (NK) cell regulators, bind HLA class-I molecules or still unknown ligands. Interest in

KIR genotyping is increasing because of the importance of these receptors for identifying

the best possible donor in hematopoietic stem cell transplantation to obtain a graft-versus-

leukemia effect. Currently, routine protocols to determine the gene content of the KIR

cluster are exclusively performed by PCR-SSO and PCR-SSP.

To improve the study of these genes, we developed a multiplex, long-range PCR strategy

suitable for simultaneous, high-resolution HLA class I and KIR genotyping by next

generation sequencing (NGS). This protocol allows amplification of the 14 KIR genes, 2

KIR pseudogenes, and HLA class I genes, with subsequent sequencing on an Illumina

platform. The bioinformatics analysis for KIR genotyping was performed by virtual

hybridization of gene-specific probes, and HLA genotyping was done by GenDx

NGSengine software. To validate the method reliability, 192 genomic DNA samples

previously characterized by PCR-SSO and NGS for KIR and HLA respectively were used.

When a specific KIR gene was present, a large number of gene-specific virtual probes

were detected, whereas when it was absent, very few or none were found, enabling cutoff

establishment. Concordance for both the KIR and HLA assignments as compared with the

previous characterization was 100%. In conclusion, the multiplex PCR NGS-based

strategy presented could provide an efficient, less costly method for KIR-ligand genotyping

by gene presence/absence. Furthermore, allele resolution will be possible when KIR-

specific software becomes available

www.sci.cat 43

Posters


19 Optimització de la teràpia amb Eculizumab

Mar Morral Puigmal1,5,6

; Lorena Santulario4,5

; Natàlia Ramos Terrades3,5

; Gema Ariceta Iraola2,5

;

Manuel Hernández-González1,5,6

; Romina Dieli-Crimi1,5,6

1Servei d'Immunologia,

2Servei de Nefrologia Pediàtrica,

3Servei de Nefrologia,

4Servei de Farmàcia,

5Hospital Universitari Vall d'Hebron,

6Institut de Recerca Vall d'Hebron

L’eculizumab (Soliris®, Alexion Pharmaceuticals)és un fàrmac biològic que bloqueja la

cascada d’activació del complement a nivell de C5. Aquest fàrmac actualment s’administra

com a tractament de malalties com el síndrome hemolític urèmic atípic i la

glomerulonefritis C3. Hi ha evidències d’estudis previs que demostren que els pacients

tractats amb eculizumab estan sobre-dosificats. Degut a l’alt preu del tractament, caldria

esbrinar si la concentració sèrica de fàrmac recomanada és la real en la cohort de

pacients tractats a l’Hospital Universitari Vall d’Hebron (HUVH).

En el present treball, s’ha posat a punt una tècnica d’ELISA tipus sandwich in house per

determinar la concentració del fàrmac en 14 pacients tractats a l’HUVH. La tècnica s’ha

dut a terme amb l’aparell DS2® 2-Plate ELISA Processing System (Dynex tecnologies).

S’ha estudiat la correlació amb les següents variables: pes del pacient, plaquetes,

hemoglobina, creatinina sèrica i en orina, proteïnúria i microalbuminúria, i també el nivell

de bloqueig de l’activitat del complement mitjançant la determinació del CH50 (The

Binding Site).

Hem trobat una correlació significativa negativa (r=-0,4181, p=0,00125) entre la

concentració de fàrmac i el pes dels pacients, i que els pacients es poden dividir en tres

grups: els pacients adults, amb una concentració sèrica d’eculizumab inferior a la

recomanada (50-100 μg/mL), un grup dins de la concentració recomanada, i pacients

pediàtrics amb una concentració > 100 μg/mL. No podem afirmar que els pacients amb

concentració < 50 μg/mL estiguin rebent un tractament insuficient, degut a que els

resultats amb les tècniques convencionals per estudiar l’activitat del sistema del

complement (CH50) mostren bloqueig.

Per tant, la monitorització dels nivells d’eculizumab és necessària per ajustar el tractament

d’una forma personalitzada. En futurs estudis s’haurien d’utilitzar mètodes més sensibles

per avaluar la funció del complement, com ampliar el seguiment dels pacients en el temps.

44 www.sci.cat

Posters Diagnostic Immunology 20 - 21 The authors will attend the poster on 15/11/2018: 17:00h; 16/11/2018: 11:00h, 13:30h, 16:30h.

20 The PIDCAP project: a computer-based algorithm for PID

screening in primary care

Marina García-Prat1,2

; Jacques G. Rivière1,2

; Andrea Martín-Nalda1,2

; Miriam González-Amores1,2

;

Diego Van Esso Arbolave3; Carlos Rodrigo

4; Pere Soler-Palacín

1,2,4

1Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron(HUVH),

2Jeffrey Modell Excellence Centre.Barcelona, Spain.,

3Catalan Institute of Health, Primary Care Health

Centre Service Muntanya-Barcelona, Barcelona, Spain, 4Pediatrics department, Hospital Universitari Vall

d’Hebron. Barcelona, Spain., 5Catalan Institute of Health, Primary Care Health Centre Service Carmel-

Barcelona, Barcelona, Spain.

Background: Primary immunodeficiencies (PID) are underdiagnosed diseases worldwide.

Diagnosis delay is linked to poor prognosis. Initiatives like the 10 Jeffrey Modell

Foundation’s warning signs (WS) help primary care physicians to detect PID. Computer-

based algorithms like the USA-based project SPIRIT® have shown relatively good results.

The aim of the PIDCAP project is to develop a computer-based algorithm using WS and

International Classification of Diseases 10th edition together with an educational program

to increase awareness of PID in primary care setting.

Methods: Literature search was performed seeking described WS for PID, their limitations

and new non-infectious WS. We selected 26 pediatric and 23 adult WS, respectively.

Numerical score was assigned to each WS and a cut-off (>75 points) was established

based on the opinion of 47 Spanish PID experts. The computer-based algorithm was

included in the primary care E-Health Record system of a pilot area of 97,000 patients.

When positive, an alert is sent to general practitioners or paediatricians who actively

evaluates the need for immunological studies.

Results: The algorithm was applied to 15,150 pediatric and 81,850 adult patients: 1190

(14.5:1000) adults and 67 (4.4:1000) pediatric patients were detected as high risk for PIDs.

Bronchiectasis and severe infections were the two WS leading to screening in adult and

pediatric patients, respectively. Full results will be shortly available.

Conclusions: PIDCAP is a computer-based algorithm for PID screening using modified

classic WS. This will improve PID detection in primary care settings besides increasing its

awareness.

www.sci.cat 45

Posters Diagnostic Immunology 20 - 21 The authors will attend the poster on 15/11/2018: 17:00h; 16/11/2018: 11:00h, 13:30h, 16:30h.

21 Characterization of T-cell receptor alpha/beta CD4-CD8-double-

negative T cells in a patient with a novel somatic heterozygous

mutation in FAS

Mónica Martínez-Gallo1; Pablo Velasco

2; Gemma Vila-Pijoan

1; Marina García-Prat

3; Pere Soler-

Palacín3; Laura Viñas-Giménez

1; Clara Franco-Jarava

1; Andrea Martín-Nalda

3; Roger Colobran

1; José

Luis Dapena2

1Immunology Division, Vall d’Hebron University Hospital (HUVH), Barcelona, Spain,

2Service of Paediatric

Haematology and Oncology, Hospital Universitari Vall d'Hebron (HUVH), Barcelon, 3Pediatric Infectious

Diseases and Immunodeficiencies Unit (UPIIP), Hospital Universitari Vall d'Hebron.

Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare genetic disorder of

lymphocyte homeostasis. This was first recognized in 1967 by Canale and Smith and is

now defined as a chronic (> 6 months) nonmalignant disease and noninfectious

lymphoproliferation frequently accompanied by autoimmune cytopenias. Accumulation of

CD3+ T-cell receptor (TCR) alpha/beta CD4-CD8-double-negative T cells (DNT) is a

distinctive feature of ALPS.

We present a 12-month-old baby boy with bicytopenia (thrombocytopenia (platelet count:

93.000/mm3), anemia (haemoglobin: 8.3 mg/dl)), massive splenomegaly /hepatomegaly

who was admitted in our center for febrile syndrome. The patient has a normal

pondostatural and psychomotor development and there is no family history. Results of

microbiological tests were negative.

The lymphocyte population analysis showed a 7% DNT population with serum IgG of 1882

mg/dL (196-1045mg/dL), high plasma levels of IL-10 peaked at 123 ng/mL (0-7.8ng/mL)

and vitamin B12 levels >2000pg/mL (211-911 pg/mL).

An extended lymphocyte study has been performed to characterize the DNT

subpopulation which reached up to 30% of the lymphocytes. The phenotype of the DNT

subpopulation shows co-expression of CD57, CD27, FAS, HLA-DR and perforin markers.

Regarding B subpopulations no alterations were observed.

The combination of clinical findings, positive serological markers (VitB12, IL10,

hypergammaglobulinemia) and a compatible lymphocyte phenotype led to perform the

study of germinal mutations in FAS, CASP10 and CASP8 genes, which did not show any

pathogenic variants. Double negative T cells were subsequently isolated by flow cytometry

cell sorting and a novel heterozygous dominant FAS mutation (c.718_719insGTCG) was

detected in a fraction of the DNT cells (<50%).

The patient was treated with the rapamycin inhibitor (sirolimus) which controlled the

disease until normalization of cytopenias and splenomegaly with a significant decrease in

the double negative population. Phenotypic characterization and monitoring of the DNT

population allows a better follow-up in response to treatment.

46 www.sci.cat

Posters Immune Response 22 - 28 The authors will attend the poster on 15/11/2018: 17:00h; 16/11/2018: 11:00h, 13:30h, 16:30h.

22 Phosphatidylserine-Liposomes render tolerogenic Dendritic

cells from adult and paediatric patients with type 1 Diabetes

through apoptotic mimicry

Silvia Rodríguez-Fernández1; David Perna-Barrull

1; Irma Pujol-Autonell

1; Mary Cano-Sarabia

2;

Federico Vázquez3; Marta Murillo

4; Adrian Villalba

1; Joan Bel

4; Joan Verdaguer

5,6; Daniel Maspoch

2,7;

Marta Vives-Pi1,6

1Immunology Section, Germans Trias i Pujol Research Institute, UAB, Badalona, Spain,

2Catalan Institute of

Nanoscience and Nanotechnology, Bellaterra, Spain, 3Endocrinology Section, Germans Trias i Pujol

University Hospital, Badalona, Spain, 4Paediatric Section, Germans Trias i Pujol University Hospital,

Badalona, Spain, 5Department of Experimental Medicine, University of Lleida IRBLleida, Lleida, Spain,

6CIBERDEM, ISCIII, Barcelona, Spain,

7ICREA, Barcelona, Spain.

The re-education of the immune system is essential for tackling type 1 diabetes (T1D), a metabolic

disease resulting from the autoimmune destruction of beta-cells. Since apoptotic cell clearance

(efferocytosis) constitutes an efficient mechanism in inducing self-tolerance, we designed a

nanotherapy consisting of phosphatidylserine (PS)-rich liposomes encapsulating beta-cells

autoantigens to mimic apoptotic beta-cells. PS-liposomes rendered dendritic cells (DCs)

tolerogenic after being phagocyted, arrested autoimmune destruction and prevented experimental

T1D (non-obese diabetic model) and multiple sclerosis (experimental autoimmune

encephalomyelitis-induced model). To move forward, this study aimed to validate the effect of PS-

liposomes in DCs from adult and paediatric patients with T1D. To that end, PS-liposomes loaded

with human insulin peptides as autoantigens were generated with optimum size and composition

for DCs phagocytosis. Peripheral blood samples were obtained for monocyte isolation and further

in vitro differentiation to DCs. Presence of PS prompted optimal liposome phagocytosis kinetics,

which was similar in the adults’ patient and control groups. Remarkably, DCs from paediatric

patients at onset captured PS-liposomes more efficiently than DCs from paediatric patients at 1-3

years after diagnosis. PS-liposomes had no detrimental effect on DCs’ viability, although their

phenotypic profile was modulated, as evidenced by decreased expression of efferocytosis

receptors and preserved low levels of adhesion, antigen-presenting, activation and costimulatory

molecules. After PS-liposomes uptake, DCs showed anti-inflammatory cytokine secretion and

impaired ability to stimulate autologous T-lymphocyte proliferation. Furthermore, the transcriptomic

analysis revealed differential expression of several immunoregulationrelated genes in DCs after

PS-liposomes engulfment. In conclusion, phagocytosis of apoptotic-mimicking PS-liposomes

induced a tolerogenic phenotype and functionality in DCs, thus validating the tolerogenic effect

prompted in NOD mice. As PS-liposomes call for apoptotic cell clearance, a physiological and

memory-inducing approach, these results reinforce the potential of this biomimicry-based antigen-

specific immunotherapy to arrest autoimmune reactions.

Funding: ISCIII (PI15/00198); AGAUR, GenCat; Fundación DiabetesCero.

www.sci.cat 47

Posters Immune Response 22 - 28 The authors will attend the poster on 15/11/2018: 17:00h; 16/11/2018: 11:00h, 13:30h, 16:30h.

23 PF4 implication in the immunosuppressive microenvironment

of Malignant Pleural Effusion

Maria Mulet1; Carlos Zamora

1; Juan C. Nieto

1; José M. Porcel

2; Elisabet Cantó

1; M. Angels Ortiz

1;

Lidia Perea1; Virginia Pajares

3; Ana Muñoz

3; Nuria Calvo

4; Iñigo Espinosa

5; Mónica Pascual

5; Silvia

Bielsa2; Silvia Vidal

1

1Dep. Experimental Immunology, Institut Recerca Hospital de La Santa Creu i Sant Pau, Barcelona,

2Pleural

Medicine Unit, Dep. Internal Medicine, Hospital Arnau de Vilanova, Lleida, 3Dep. Pneumology, Hospital de

La Santa Creu i Sant Pau, Barcelona, 4Dep. Oncology, Hospital de La Santa Creu i Sant Pau, Barcelona,

5Dep. Pathology, Hospital de La Santa Creu i Sant Pau, Barcelona.

Background: Malignant pleural effusion (MPE) is defined as the accumulation of tumor

cells in the pleural fluid and it is a common complication of advanced lung cancer.

Adenocarcinoma is the main type of cancer that causes metastasis in the pleural cavity.

Among cytokines that participate in this characteristic pro-tumor microenvironment, we

have described that PF4 levels were higher in MPE and it was related with a poor

prognosis in these patients.

Aim: Our general aim was to compare the effect of pleural fluid from adenocarcinoma

patients and from congestive heart failure (as control) on the T lymphocyte function.

Especially, we hypothesize that PF4 could act as a pro-tumor factor implicated in the

immunosuppressive microenvironment of MPE.

Methods: PBMCs from healthy donors were labeled with CFSE, stimulated and cultured

with medium supplemented with heart failure (HF) or lung cancer (LC) pleural fluids for

72h. PBMCs were also cultured in the presence of recombinant human PF4. In both

cultures, proliferation and cytotoxic phenotype of T lymphocytes were determined by flow

cytometry. Pleural fluids and culture supernatants were analyzed for cytokine content

(PF4, IL-10 and IFN-γ) by ELISA.

Results: We validated in a new cohort of patients that levels of PF4 were significantly

higher in pleural fluids from LC patients than in HF. The presence of MPE inhibited the T

lymphocyte proliferation. Not only the proliferation but also the cytotoxic phenotype were

inhibited when T lymphocytes were cultured in the presence of PF4. This molecule also

tended to bias T cell response towards a non-inflammatory profile, increasing IL-10 levels.

Conclusions: The high content of PF4 in the MPE may be responsible for the modulation

of the immune response against the tumor. An impaired proliferative and cytotoxic

response of T lymphocytes induced by PF4 could provide a significant advantage for the

tumor to progress.

48 www.sci.cat

Posters Immune Response 22 - 28

The authors will attend the poster on 15/11/2018: 17:00h; 16/11/2018: 11:00h, 13:30h, 16:30h.

24 Potentiation of mucosal IgA production by a multivitamin and

fibre supplement in adults rats

Malen Massot-Cladera1; Ignasi Azagra-Boronat

1; Àngels Franch

1; Margarida Castell

1; Maria J.

Rodríguez-Lagunas1; Francisco J. Pérez-Cano

1

1Dept de Bioquímica i Fisiologia, Fac. de Farmàcia i Ciències de l’Alimentació (Universitat de Barcelona);

INSA-UB.

Introduction: Supplementation with dietary fibers can modulate both the intestinal

immune system and the intestinal microbiota composition1.

Objective: Therefore, the aim of this study was to establish the effects of two multivitamin

supplements enriched with two different dietary fibers on the intestinal immune system in

adult rats, specifically on IgA production.

Methods: For this purpose, 9-week-old female and male Wistar rats were distributed into

four experimental groups (n=10/group): one constituted the REF group, another group

received a daily vitamin supplement (V), and two other groups received this supplement

enriched with inulin (V+I) or acacia fiber (V+A). After four weeks, fecal samples were

collected to quantify the IgA by ELISA and to determine the proportion of IgA-coated

bacteria by flow cytometry analysis. At the same time point, small intestine was collected

to obtain the gut lavage for IgA quantification.

Results: Both the V+I and V+A supplementations increased the concentration of the IgA in

fecal samples but only the increase after inulin-enriched supplement (V+I) reached the

significance compared to both the REF and V groups (p<0.05). However, no changes on

either gut wash IgA concentration or the proportion of bacteria coated to IgAwere

observed.

Conclusions: Overall, from both supplements tested in the present study, only the V+I

was the one that showed intestinal immune enhancement properties in adult rats.

Acknowledgements: The authors would like to thank Mara Carmona and Alex Llorca for

their technical assistance. 1 Slavin J. Fiber and prebiotics: mechanism and health benefits. Nutrients 5(4);1417-35.

www.sci.cat 49



25 Alterations in the spleen immune function due to overtraining

and an exhaustive exercise in rats

Patricia Ruiz-Iglesias1; Sheila Estruel-Amades

1; Malen Massot-Cladera

1; Pau García-Cerdà

1; Àngels

Franch1; Francisco J. Pérez-Cano

1; Margarida Castell

1; Mariona Camps-Bossacoma

1

1Dept de Bioquímica i Fisiologia, Fac. de Farmàcia i Ciències de l’Alimentació (Universitat de Barcelona);

INSA-UB.

High-intensity physical exercise and overtraining has been shown to decrease immune

system functionality. Therefore, the risk of infection diseases such as upper respiratory

tract infections rises during periods of high intensity training and exhausting competitions

(1). The aim of this study was to establish the influence of overtraining and an additional

exhausting exercise (AEE) on spleen lymphocyte composition and functionality in rats.

For this purpose, 4-week-old female Wistar rats were submitted to high-intensity exercise

training or remained as a sedentary control group. The exercised group undertook high-

intensity endurance training on a treadmill 5 days per week (including 2 exhausting tests)

for 5 weeks. At the end, samples were obtained after overtraining (before performing the

AEE), immediately after the AEE and 24 h later to assess the spleen lymphocyte

composition and functionality.

Concerning lymphocyte composition, both overtraining and the AEE reduced spleen NK

and NKT cell proportions. In addition, overtraining raised the proportion of spleen TCRαβ+

cells, mainly due to an increase in the TCRαβ+CD8+ subset. Overtraining also tended to

decrease T-cell proliferative capacity and reduced IFN-γ secretion whereas increased that

of IL-6. Immediately after performing the AEE, splenocytes proliferation rate increased but

decreased 24 h later. Moreover, the AEE diminished in vitro IgM and IgG secretion by

spleen cells.

In conclusion, the overtraining and the additional exhausting exercise tested in our study

induced alterations in spleen functions which could contribute to the depression of

immunity and the higher risk of infection diseases typical of high-intensity endurance

training periods.

References (1) Walsh NP. Recommendations to maintain immune health in athletes. Eur

J Sport Sci. 2018;1–12.

50 www.sci.cat



26 Spleen lymphocyte composition is modulated by breast milk

growth factors

Paulina Torres-Castro1,2

; Blanca Grases-Pintó1,2

; Mar Abril-Gil1,2

; Margarida Castell1,2

; María J.

Rodríguez-Lagunas1,2

; Francisco J. Pérez-Cano1,2

; Àngels Franch1,2

1Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of

Barcelona (UB), 2Nutrition and Food Safety Research Institute (INSA·UB).

Neonatal immune responses are functionally deficient and less competent compared to

adults, increasing the risk of infections. Breast milk is a rich fluid containing bioactive

compounds that contribute to the maturation of the immune system in early life such as

specific growth factors.

The aim of this study was to determine whether transforming growth factor (TGF)‑β2,

epidermal growth factor (EGF) and fibroblast growth factor 21 (FGF21), compounds

present in breast milk, were able to influence the spleen lymphocyte composition during

the suckling period.

For this purpose, newborn Wistar rats were daily supplemented by oral gavage during the

suckling period (21 days of life). Reference group received vehicle, and TGF-β2, EGF and

FGF21 groups received the respective commercial product. On days 14 and 21, spleen

cell composition was established by immunofluorescence staining and flow cytometry

analysis.

In suckling rats’ spleen, B cells constituted the main lymphocyte population followed by

TCRαβ+ and NK cells, and in less proportion TCRγδ+ and NKT cells. The proportions of

these lymphocytes were modified by EGF and FGF21 supplementation but not by TGF-β2.

At day 14, the supplementation with EGF was able to promote the development of B cells,

by increasing its proportion up to levels found in 21-day-old rats. Moreover, EGF

accelerated the physiological reduction in the proportion of the immature NK CD8+ cell

subset. Regarding day 21, the supplementation with EGF and FGF21 did not promote

maturation, however they induced a significant decrease in the proportion of the main cell

subsets such as T, NKT, CD8+ and CD4+ lymphocytes.

These results demonstrate that the supplementation with breast milk growth factors,

mainly EGF, can modify the spleen lymphocyte composition suggesting its contribution to

the maturation of the systemic immune system in early life.

www.sci.cat 51



27 Leptin and epidermal growth factor influence mesenteric

lymph node cell maturation in preterm rats

Blanca Grases-Pintó1,2

; Paulina Torres-Castro1,2

; Mar Abril-Gil1,2

; María José Rodríguez-Lagunas1,2

;

Margarida Castell1,2

; Francisco José Pérez-Cano1,2

; Àngels Franch1,2

1Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, University of

Barcelona (UB), 2Institut de Recerca en Nutrició i Seguretat Alimentària (INSA·UB).

In preterm newborns the immaturity of the immune system is remarkable, with reduced

innate and adaptive immune response. Many bioactive compounds in breast milk, such as

growth factors and adipokines, contribute to the immune system maturation in early life.

However, studies on their immunoregulatory activity in preterm neonates are practically

nonexistent

The aim of the present study was to determine whether a nutritional supplementation in

early life with leptin or epidermal growth factor (EGF), both immunomodulatory molecules

present in breast milk, was able to promote maturation of mesenteric lymph node (MLN)

cells in preterm rats.

For this purpose, premature pups were delivered by a caesarean section one day before

the physiological time of delivery. Then, animals were daily supplemented by oral gavage

with leptin or EGF during the first 17 days of life. Preterm and term groups receiving

vehicle were used as controls. At day 17, MLN lymphocytes were isolated and their

composition was established by immunofluorescence staining and flow cytometry analysis.

Pups born prematurely showed higher T cell and lower B cell proportions, in comparison to

term rats. EGF, but not leptin supplementation, was able to reverse this situation,

decreasing T cell and increasing B cell percentages compared to preterm group. Although

no changes were found in TCRγδ+ and NKT cells, an increase in the NK cell proportion

due to EGF supplementation was detected. Moreover, both bioactive components

decreased CD8+ cell proportion, whereas only EGF additionally decreased CD4+ cell

percentage, in comparison to preterm control rats.

Overall, these results suggest that leptin and EGF are relevant breastmilk components

promoting the mesenteric lymph node cells maturation in preterm conditions.

52 www.sci.cat



28 Effects of Mesenchymal Stem Cells (MSC) on the

degranulation of purified CD8 lymphocytes

Carla Panisello Aranda1; Pascual Martínez-Peinado

2; Mónica Martínez-Gallo

1

1Immunology Division, Hospital Universitari Vall d’Hebron HUVH, Vall d’Hebron Research Institute VHIR,

2Immunology Division, Departamento de Biotecnología, Universidad de Alicante.

Introduction: Mesenchymal stem cells are a widely used population in cell therapy

because of their ability to immunomodulate immune system responses. Among these

responses, MSCs are able to decrease the degranulation of NK cells, but there are very

few studies focusing on the degranulation of purified CD8 T lymphocytes. In addition, in

previous studies we demonstrated MSCs increases the proliferation of these purified

lymphocytes, contrary to what usually occurs when total lymphocyte populations are

analyzed.

Matherials and Methods: We conducted proliferation assays of CD8 purified

lymphocytes, with MSC (ratio 1:10, MSC:lymphocytes) or their conditioned media (MSC-

CM) with CFSE technique. We also performed assays to analyse the effect of these MSC

and MSC-CM on the degranulation of CD8 purified lymphocytes, by detecting de CD107a

marker on the external membrane of lymphocytes. All the experiments were carried out by

flow cytometry.

Results: As expected, MSCs and their CMs did not modify the cell proliferation of purified

CD8 lymphocytes under non-stimulus conditions. In the presence of PHA, MSC-CM

inhibited this proliferation. However, in the presence of the MSCs themselves, cell

proliferation increased. Regarding degranulation assay, while the presence of MSC did not

modify the behaviour of purified CD8 lymphocytes, MSC-CM did manage to inhibit the

degranulation of these cells under stimulation conditions.

Conclusion: Considering all these results, it seems that mesenchymal cells have no effect

on the degranulation of purified CD8 lymphocytes, at least at the studied ratio. However,

their CM were able to decrease this process. On the other hand, we confirm that MSCs

increase the proliferation of purified CD8 lymphocytes, as we publish preventatively, but

surprisingly, their conditioned media cause the opposite effect.

www.sci.cat 53

Posters Innate Immunity 29 The authors will attend the poster on 15/11/2018: 17:00h; 16/11/2018: 11:00h, 13:30h, 16:30h.

29 Interrelation among rat milk bioactive components:

immunoglobulins, fatty acids and microbiota

I. Azagra-Boronat1,2

; A. Tres1,3

; M. Massot-Cladera1,2

; À. Franch1,2

; M. Castell1,2

; F. Guardiola1,3

; F.J.

Pérez-Cano1,2

; M.J. Rodríguez-Lagunas1,2

1Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Santa Coloma de Gramanet;

2Secció de

Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació; 3Departament de Nutrició, Ciències de l’Alimentació i Gastronomia, Facultat de Farmàcia i Ciències de

l’Alimentació.

Introduction: Breastmilk is an important source of immunoglobulins (Ig) which play a key

role in the passive immunization of the newborn, whose immune system’s immaturity is

unable to cope with all external threads. Moreover, it is known that certain fatty acids (FA)

and bacteria have also immunomodulatory effects which may have an impact on the infant

immunity.

Objective: The objective of the present work was to study the relationship among

components present in rat milk with immunomodulatory potential: Ig, FA and microbiota.

Methodology: Pregnant Wistar rats (n=6) were allowed to deliver at term, unified to 8

pups/lactating dam and monitored daily. Milk samples were collected two weeks after

delivery to quantify Ig by flow cytometry immunobead-assay, the content of FA by GC-FID,

and the milk microbiota composition by 16S rRNA sequencing.

Results: The milk of 14-day lactating rats was dominated by IgGs, most specially IgG2b

and IgG2c along with a high content of IgA. In regard to FA composition, 64% of the FA

were saturated, 16% monosaturated and 20% polyunsaturated. The milk microbiome was

dominated by Proteobacteria and Firmicutes members, being Pasteurella, Streptococcus

and Rodentibacter the most abundant genera. Moreover, the amount of several Ig

correlated with certain FA or bacteria. For example, linoleic acid and Lachnoclostridium

correlated positively with the amount of IgG2a, which is associated with a Th2 response,

whereas total saturated fatty acids and gamma linolenic correlated negatively. Contrarily,

the amount of Enterobacter in milk correlated with Ig isotypes associated with a Th1

response, such as IgG2b and IgG2c.

Conclusions: We have stablished the correlation of Ig present in rat breastmilk with other

factors such as FA and bacteria. Nutritional interventions during gestation or pregnancy

that affect the breast milk FA or microbiota composition could also be directed to influence

infant’s passive immunity.

54 www.sci.cat

2019 Events

Lifelong Learning SCI Program 2019

Data i hora: 7 de febrer de 2019, a les 18.30h

Heterogeneïtat de la resposta immune al pulmó: tabac i malaltia obstructiva crònica.

Dra. Rosa Faner (Hospital Clínic, Barcelona, ES).

Lloc: Sala 9, Acadèmia de Ciències Mèdiques (Major de Can Caralleu 1-7, Barcelona).

Data i hora: 7 de març de 2019, a les 18.30h

Immunologia del Transplantament d’òrgan sòlid (Taula Rodona).

Dr. Jaume Martorell (Hospital Clínic, Barcelona, ES), Dr. Eduard Palou (Hospital Clínic,

Barcelona, ES), Dra. Marcela Franquesa (Institut Germans Trias i Pujol, Badalona, ES).


Data i hora: 25 d’abril de 2019, a les 15.00h

Sepsis: Challenges and new perspectives. DIA DE L’IMMUNOLOGIA.

Dr. Antonio Artigas (Dept. de Medicina, UAB, ES), Dr. Francisco Lozano (Dept. de

Biomedicina, UB, ES), Dr. Rafael Máñez (Institut d'Investigació Biomèdica de Bellvitge,

(IDIBELL), ES).


Data i hora: 2 de maig de 2019, a les 18.30h

Myeloid-derived-suppressor cells.

Dr. Jordi Ochando (Mount Sinai, New York, US).


Data i hora: 6 de juny de 2019, a les 18.30h

Aplicaciones de nanopartículas superparamagnéticas de óxido de hierro en

inmunoterapia contra el cáncer.

Dr. Domingo Francisco Barber (Centro Nacional de Biotecnología, CSIC, Madrid, ES).


www.sci.cat 55

New members Registration form to SCI

56 www.sci.cat

Participant information: useful information

Congress Venue: Academia de Ciències Mèdiques, Auditori de l’Acadèmia c/ Major de Can Caralleu1 08017 Barcelona. Transportation:

By car: Ronda de Dalt, exit 9

By bus: o Line 66 (Pl. Catalunya – Sarrià) o Line 60 (Pl. Glòries – Zona Universitaria) o Line V3 (Zona Franca –Can Caralleu) o Line 130 (Pl. Artós – Can Caralleu))

By subway: Ferrocarrils de la Generalitat de Catalunya (FGC): Line 6: Reina Elisenda station Parking: Small open area between the Academy and the city ring (only for members of the Academy: Parking fees apply). Congress Office:

Sr. Xavier Nieves Tel: 00 34 93.203.13.18 ; FAX: 00 34 93 212 35 69 [email protected]

mailto:[email protected]

www.sci.cat 57

List of participants and authors

Abril-Gil M. ........................................................... 50, 51 Aguilera E. .................................................................. 25 Aguiló-Cucurull A. ...................................................... 39 Aksentijevich I. ........................................................... 16 Alfaro C. ..................................................................... 19 Alperi-López M. .......................................................... 11 Alserawan L. ........................................................ 26, 28 Alsina L. ..................................................................... 23 Álvarez A. ................................................................... 12 Álvarez D. ................................................................... 16 Àlvarez-Sierra D. ........................................................ 39 Ampudia RM. ....................................................... 18, 25 Antolín M. ................................................................... 12 Aparici I. ..................................................................... 17 Ara del Rey J. ............................................................. 10 Argudo A. ................................................................... 13 Ariceta G. ................................................................... 43 Arméstar F. ................................................................ 14 Arroyes M. .................................................................. 29 Aterido A. ............................................................... 5, 11 Azagra-Boronat I. ................................................. 48, 53 Balagué O. ................................................................... 9 Barba P. ..................................................................... 35 Bas J. ............................................................. 36, 37, 38 Bassolas H. ................................................................ 29 Baucells A. ................................................................. 28 Baumann T. .................................................................. 9 Bel J. .......................................................................... 46 Benítez D. .................................................................... 9 Bielsa I. ...................................................................... 34 Bielsa S. ..................................................................... 47 Blanco F. .................................................................... 11 Blasco L. .................................................................... 12 Bodet D. ..................................................................... 16 Boera-Carnicero G. .................................................... 26 Boronat A. .................................................................... 9 Borràs F. ...................................................................... 6 Bragado I. ................................................................... 21 Brieva L. ..................................................................... 33 Briongos-Sebastian S................................................. 39 Bueno C. ...................................................................... 9 Buschow SI. ............................................................... 19 Caballero M. ................................................................. 9 Caicedo M. ................................................................. 30 Calvo N. ..................................................................... 47 Camins J. ................................................................... 31 Campo E. ..................................................................... 9 Campos D. ................................................................. 24 Camps-Bossacoma M. ............................................... 49 Canals JM. ................................................................... 9 Cano A. ...................................................................... 33 Cano-Sarabia M. ........................................................ 46 Cantó E. ..................................................................... 47 Cañete JD. ................................................................. 11 Caro JL. ...................................................................... 42 Castaño J. .................................................................... 9 Castell M. ............................................ 48, 49, 50, 51, 53 Castella M. ................................................................... 9 Celada A. ......................................................... 6, 15, 17 Cid J. ............................................................................ 9 Cidó L. ........................................................................ 11

Clark A. ....................................................................... 24 Climent J..................................................................... 38 Closa L. ...................................................................... 42 Coll M. ........................................................................ 38 Colobran R. ........................................ 12, 13, 16, 39, 45 Coma M. ..................................................................... 25 Corominas H. .............................................................. 11 Corraliza A. ................................................................. 29 Cortés-Hernández J. .................................................. 40 Costa C. ....................................................................... 7 Cuenca M. .................................................................. 22 Dapena JL. ................................................................. 45 de la Calle O. .............................................................. 28 de Vries JM................................................................. 19 Delgado J. .................................................................... 9 Depreux N. ................................................................. 34 Deyà-Martínez A. ........................................................ 23 Diekmann F. ............................................................... 41 Dieli-Crimi R. .................................................... 5, 12, 43 Digón M. ..................................................................... 27 Domingo S. ................................................................. 40 Egri N. .................................................................. 27, 41 Ehrenberg C. .............................................................. 25 Elias N. ....................................................................... 15 Engel P. .................................................................. 9, 22 Erra A. ........................................................................ 11 Espin E. ...................................................................... 24 Espinosa G. ................................................................ 30 Espinosa I. .................................................................. 47 Esteller M.................................................................... 29 Esteve C. .................................................... 5, 10, 31, 32 Esteve-Solé A. .................................................. 7, 23, 30 Estruel-Amades S. ...................................................... 49 Faner R. ....................................................................... 7 Fernández MD. ........................................................... 41 Fernández-Gutierrez B. .............................................. 11 Fernández-Nebro A. ................................................... 11 Ferrer B. ..................................................................... 40 Flórez G. ................................................................. 7, 19 Franch A. ............................................ 48, 49, 50, 51, 53 Franco T. .............................................................. 26, 28 Franco-Jarava C. ............................ 6, 12, 13, 16, 39, 45 Gala G. ....................................................................... 39 García E. .................................................................... 39 García M. .................................................................... 30 García MJ. .................................................................. 37 García-Cerdà P. ......................................................... 49 García-Latorre L. ........................................................ 16 García-Patos V. .......................................................... 16 García-Prat M. ................................ 5, 13, 16, 39, 44, 45 Garrido A. ................................................................... 29 Gieras A. .................................................................... 18 Glau L. ........................................................................ 18 Goma M. ..................................................................... 36 González A. ................................................................ 11 González I. ................................................................. 11 González JM............................................................... 13 González-Amores M. .................................................. 44 González-Navarro EA. ............................................ 9, 30 Grases-Pintó B. .................................................... 50, 51 Graterol FA. ................................................................ 10

58 www.sci.cat

Grau-Vorster M. ......................................................... 35 Guardiola F. ............................................................... 53 Hernández-González M. ................................ 13, 39, 43 Hernández-Lafuente MC. ........................................... 26 Herrera C. .................................................................. 24 Herrero MJ. ................................................................ 42 Holgado S. ................................................................. 31 Jaraquemada D. ........................................................... 7 Juan M. .............................................................. 5, 9, 23 Juarez C. .................................................................... 26 Julià T......................................................................... 11 Landolfi S. .................................................................. 24 Lázaro A. .................................................................... 22 Lleixà MC. .................................................................. 26 Llobell A. .................................................................... 30 Lloberas J. ............................................................ 15, 17 López CA. .................................................................. 34 López D. ..................................................................... 32 López M. .................................................................... 11 López RM. .................................................................. 13 López-Lasanta M. ...................................................... 11 López-Montañes M. ................................................... 35 López-Serrat M. ......................................................... 17 Lozano F. ..................................................................... 6 Lozano M. .................................................................... 9 Lucas E. ................................................................. 6, 14 Luo Y. ......................................................................... 23 Machiels K. ................................................................. 24 Manchón A. ................................................................ 27 Manichanh C. ............................................................. 24 Mansilla MJ. ................................................7, 20, 21, 33 Marín JL. .................................................................... 13 Maroto J. .................................................................... 35 Marsal S. .................................................................... 11 Martí M. ...................................................................... 24 Martínez M. .......................................................... 31, 32 Martínez-Cáceres EM. .. 5, 10, 14, 20, 21, 31, 32, 33, 34 Martínez-Gallo M. ................................ 12, 13, 39, 45, 52 Martínez-Martínez L. ............................................ 26, 28 Martínez-Peinado P. .................................................. 52 Martínez-Taboada V. ................................................. 11 Martín-Ibáñez R. .......................................................... 9 Martín-Nalda A. ............................. 12, 13, 16, 39, 44, 45 Martorell J. ................................................................. 27 Martos S. .................................................................... 39 Marzal B. ...................................................................... 9 Mas V. .........................................................5, 36, 37, 38 Masamunt MC. ........................................................... 29 Maspoch D. .......................................................... 25, 46 Massot-Cladera M. ......................................... 48, 49, 53 Mathan TSM. .............................................................. 19 Maymó J. .................................................................... 11 Melero I. ..................................................................... 19 Menéndez P. ................................................................ 9 Molero X. .................................................................... 12 Moliné T. .................................................................... 40 Moltó-Lacosta E. ........................................................ 26 Montserrat I. ............................................................... 39 Moral-Torres E. .......................................................... 33 Morandeira F. ................................................. 36, 37, 38 Morral M. .................................................................... 43 Moya C. ...................................................................... 35 Mulet M. ..................................................................... 47 Munteis E. .................................................................. 33 Muñoz A. .................................................................... 47 Murillo M. .................................................................... 46 Naranjo-Gómez M. ..................................................... 20

Navarro MI. ........................................................... 10, 32 Navarro S. ............................................................ 36, 37 Navarro-Barriuso J. .................................... 7, 20, 21, 33 Nieto JC. ..................................................................... 47 Notario J. .................................................................... 38 Olivè A. ....................................................................... 11 Ordi-Ros J. ................................................................. 40 Ortiz de Landazuri I. ................................................... 27 Ortiz MA. .................................................................... 47 Ortiz-Maldonado V. ....................................................... 9 Padullés N. ................................................................. 38 Pajares S. ................................................................... 13 Pajares V. ................................................................... 47 Palou E. ................................................................ 27, 41 Panés J. ..................................................................... 29 Panisello C. ................................................................ 52 Paramonov I. .............................................................. 12 Pascual M. .................................................................. 47 Perea L. ...................................................................... 47 Pérez R. ..................................................................... 28 Pérez-Cano FJ. .................................. 48, 49, 50, 51, 53 Pérez-Galán P. ............................................................. 9 Pérez-Isidro A. ............................................................ 30 Perna-Barrull D. .......................................... 6, 18, 25, 46 Perpiña U...................................................................... 9 Plaja A. ....................................................................... 16 Planas AM. ................................................................... 6 Plans O. ...................................................................... 14 Plaza-Martín AM. ........................................................ 23 Porcel JM:................................................................... 47 Poyatos E. .................................................................. 36 Pozuelo M................................................................... 24 Presas-Rodríguez S. ............................................ 21, 33 Prieto S. ...................................................................... 30 Pujol-Autonell I. .............................................. 18, 25, 46 Pujol-Borrell R. ......................................... 2, 5, 7, 12, 39 Puñet-Ortiz J. .......................................................... 7, 22 Querol L. ..................................................................... 26 Querol S. .................................................................... 35 Quintana LF. ............................................................... 41 Quirant-Sánchez B. ................ 10, 20, 21, 31, 32, 33, 34 Ramming A. .................................................................. 7 Ramos N..................................................................... 43 Ramo-Tello C. ................................................ 20, 21, 33 Rehues P. ................................................................... 17 Reinieren-Beeren I. .................................................... 19 Rives S. ........................................................................ 9 Rivière JG. ............................................................ 13, 44 Rodas LM. .................................................................. 41 Rodrigo C. .................................................................. 44 Rodríguez V.................................................................. 9 Rodríguez-Fernández S. ................................ 18, 25, 46 Rodríguez-Lagunas MJ. ........................... 48, 50, 51, 53 Rodríguez-Sureda V. .................................................. 16 Rubiales MV. .............................................................. 26 Rubio L. ................................................................ 30, 41 Rudilla F. .............................................................. 16, 35 Ruíz A. ........................................................................ 34 Ruiz-Iglesias P. ........................................................... 49 Ruiz-Ortiz E. ......................................................... 30, 41 Sáez M. ...................................................................... 22 Salas A. ...................................................................... 29 Salgado-Perandrés S. ................................................ 39 Sánchez-Fernández S. ............................................... 11 Sánchez-Pla A. ........................................................... 20 Sancho D. ................................................................... 19 Santamaria L. ............................................................... 5

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Santiago A. ................................................................. 24 Santulario L. ............................................................... 43 Sarrabayrouse G. ................................................... 7, 24 Sauleda S. .................................................................. 35 Saura J. ........................................................................ 6 Schreibelt G. .............................................................. 19 Semidey ME. .............................................................. 12 Serra-Pagés C. ............................................................ 9 Söhnlein O. .................................................................. 5 Solé C. ....................................................................... 40 Soler-Palacín P. .................................. 13, 16, 39, 44, 45 Soriano A. ...................................................... 10, 31, 32 Soriano L. ................................................................... 28 Suñe G. ........................................................................ 9 Tabera J. ...................................................................... 9 Teixidó I. ..................................................................... 23 Teniente-Serra A. ........................................... 20, 33, 34 Textor J. ..................................................................... 19 Tolosa E. .................................................................... 18 Tornero J. ................................................................... 11 Torras J. ..................................................................... 36 Torres-Castro P. ................................................... 50, 51 Tortosa R. .................................................................. 11 Tres A......................................................................... 53 Trias E. ......................................................................... 9

Urbano-Ispizua A. ......................................................... 9 Van Esso D................................................................. 44 van Oorschot T. .......................................................... 19 Varela E. ..................................................................... 24 Vázquez F. ........................................................... 25, 46 Velasco P. .................................................................. 45 Velásquez J. ............................................................... 12 Veny M. ...................................................................... 29 Verdaguer J. ............................................................... 46 Vermeire S.................................................................. 24 Vico T. .................................................................... 6, 15 Vidal F. ....................................................................... 42 Vidal S. ............................................................... 5, 6, 47 Vila-Pijoan G......................................................... 39, 45 Vilarrodona A. ............................................................... 9 Vilella R. ....................................................................... 9 Villalba A. ....................................................... 18, 25, 46 Viñas O. ................................................................ 30, 41 Viñas-Giménez L. ....................................................... 45 Vives-Pi M. ..................................................... 18, 25, 46 Vlagea A. .................................................................... 23 Wang H. ..................................................................... 16 Yagüe J. ................................................................. 9, 23 Yuste A. ...................................................................... 28 Zamora C.................................................................... 47

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Other useful information and notes

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XII CONGRÉS

Societat Catalana d’Immunologia (SCI)

Barcelona, 15 i 16 de novembre 2018

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