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Page 1: 2019 Advanced Track Webinars - immucor.com Program Handouts/Jolly_Slides.pdf · U N ENDA ENEV JENU Low 35 He Mia Mc Vw Mur Mg Vr Me Mt aSt Ri aCl Ny Hut Hil Mv Far sD Mit Dantu Hop
Page 2: 2019 Advanced Track Webinars - immucor.com Program Handouts/Jolly_Slides.pdf · U N ENDA ENEV JENU Low 35 He Mia Mc Vw Mur Mg Vr Me Mt aSt Ri aCl Ny Hut Hil Mv Far sD Mit Dantu Hop

2 All Content © Immucor, Inc.

Handouts

http://www.immucor.com/en-us/Pages/Educational-Program-Handouts.aspx

Page 3: 2019 Advanced Track Webinars - immucor.com Program Handouts/Jolly_Slides.pdf · U N ENDA ENEV JENU Low 35 He Mia Mc Vw Mur Mg Vr Me Mt aSt Ri aCl Ny Hut Hil Mv Far sD Mit Dantu Hop

3 All Content © Immucor, Inc.

2019 Advanced Track Webinars

Link to register: https://immucor.webinato.com/register

Page 4: 2019 Advanced Track Webinars - immucor.com Program Handouts/Jolly_Slides.pdf · U N ENDA ENEV JENU Low 35 He Mia Mc Vw Mur Mg Vr Me Mt aSt Ri aCl Ny Hut Hil Mv Far sD Mit Dantu Hop

4 All Content © Immucor, Inc.

2019 Advanced Track Webinars

Link to register: https://immucor.webinato.com/register

Page 5: 2019 Advanced Track Webinars - immucor.com Program Handouts/Jolly_Slides.pdf · U N ENDA ENEV JENU Low 35 He Mia Mc Vw Mur Mg Vr Me Mt aSt Ri aCl Ny Hut Hil Mv Far sD Mit Dantu Hop

5 All Content © Immucor, Inc.

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6 All Content © Immucor, Inc.

Link to register: https://immucor.webinato.com/register

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7 All Content © Immucor, Inc.

learn.immucor.com

Page 8: 2019 Advanced Track Webinars - immucor.com Program Handouts/Jolly_Slides.pdf · U N ENDA ENEV JENU Low 35 He Mia Mc Vw Mur Mg Vr Me Mt aSt Ri aCl Ny Hut Hil Mv Far sD Mit Dantu Hop

8 All Content © Immucor, Inc.

Continuing Education

• PACE, Florida and California DHS

• 1.0 Contact Hours

• Each attendee must register to receive CE at: https://www.surveymonkey.com/r/TheJollyBloodBanker

• Registration deadline is April 5, 2019

• Certificates will be sent via email only to those

who have registered April 19, 2019

Page 9: 2019 Advanced Track Webinars - immucor.com Program Handouts/Jolly_Slides.pdf · U N ENDA ENEV JENU Low 35 He Mia Mc Vw Mur Mg Vr Me Mt aSt Ri aCl Ny Hut Hil Mv Far sD Mit Dantu Hop

9 All Content © Immucor, Inc.

Questions?

• You are all muted

• Q&A following session - Type in questions

Page 10: 2019 Advanced Track Webinars - immucor.com Program Handouts/Jolly_Slides.pdf · U N ENDA ENEV JENU Low 35 He Mia Mc Vw Mur Mg Vr Me Mt aSt Ri aCl Ny Hut Hil Mv Far sD Mit Dantu Hop

10 All Content © Immucor, Inc.

• Course content is for information and

illustration purposes only. Immucor makes

no representation or warranties about the

accuracy or reliability of the information

presented, and this information is not to be

used for clinical or maintenance evaluations.

• The opinions contained in this presentation

are those of the presenter and do not

necessarily reflect those of Immucor.

Page 11: 2019 Advanced Track Webinars - immucor.com Program Handouts/Jolly_Slides.pdf · U N ENDA ENEV JENU Low 35 He Mia Mc Vw Mur Mg Vr Me Mt aSt Ri aCl Ny Hut Hil Mv Far sD Mit Dantu Hop

The Jolly Blood Banker and “Other” Blood Groups

Jill R. Storry, PhD FIBMS

Associate Professor, Lund University

Technical Director, Immunohematology

Clinical Immunology and Transfusion Medicine, Lund

Page 12: 2019 Advanced Track Webinars - immucor.com Program Handouts/Jolly_Slides.pdf · U N ENDA ENEV JENU Low 35 He Mia Mc Vw Mur Mg Vr Me Mt aSt Ri aCl Ny Hut Hil Mv Far sD Mit Dantu Hop

Blood systems covered in this talk:

• MNS

• Kell

• Lewis

• Duffy

• Kidd

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ABO P1PK

LewisFORSGLOB

HI

LWXg

DuffyLutheranIndian Scianna

RaphJMHOka

36 blood group systems are carried on functional molecules

Host defence/innate immunity

(Glyco)proteins of structural orunknown function

Complement regulation

Adhesion molecules

Transporters and channels

Enzymes

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The MNS Blood Group System (ISBT 002)

• MNS antigens are carried on:GPA

GPB

Hybrids of GPA & GPB

• Specific to red blood cells

• Highly polymorphic system – 49 antigens

• Function of GPA and GPB not completely understood:Chaperone proteins?

Protection by sialic acid?

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Antigens of the MNS blood group system

Prevalence n Antigens

Variable 4 M N S s

High 10 Ena ENKT ENEP ENEH ENAV

U ‘N’ ENDA ENEV JENU

Low 35 He Mia Mc Vw Mur Mg Vr Me

Mta Sta Ria Cla Nya Hut Hil Mv

Far sD Mit Dantu Hop Nob Or

DANE TSEN MINY MUT SAT ERIK

Osa HAG MARS MNTD SARA KIPP

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Numbering:

Counted from initiatingMethionine (19aa leadersequence included)

MNS antigens are carried on GPA and GPB

RBC lipid bilayer

N-linked sugarO-linked sugar

15091

20’N’

20 M/N

48 S/s

α-chymotrypsinsite at aa 51Papain site ~aa 54

Trypsin sites at aa 50 & 58Papain site at aa 78/80

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6

31 2 4 5 6

31 2 4 5 7

GYPB

GYPA

31 2 5 6

GYPE

Low nucleotide identityHigh nucleotide identity

GYPA

Chromosome 4q31.21

4

GYPEGYPB

The GYPA gene family

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Molecular Basis of MNS Antigens

Mechanisms for generating diversity:

• Single nucleotide polymorphisms (SNPs)

• Deletions/insertions

• Gene recombination events

All of the above are reported for the MNS system

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MNS SNPs

GYPB exon 4GA GAA ATG GGA CAA CTT GTC CAT CGT TTC ACT GTA CCA G S

E M G Q L V H R F T V P

GA GAA ACG GGA CAA CTT GTC CAT CGT TTC ACT GTA CCA G s

E T G Q L V H R F T V P

Single nucleotide polymorphisms are an effectivemethod of creating diversity, e.g. S/s antigens

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SNPs Encode Low Incidence Antigens

‘N’

M/N

GPA GPB

20

24

150

23 Mg

50 Or

66 Vr73 Osa76 Ria77 Mta78 ERIK82 MARS84 HAG

20

24

22 MV

54 Mit

58 sD

48 S/s

Numbering:

Counted from initiatingMethionine (19aa sequence included

46 Nya47 Vw/Hut

36 MNTD

91

SARA 80

Page 21: 2019 Advanced Track Webinars - immucor.com Program Handouts/Jolly_Slides.pdf · U N ENDA ENEV JENU Low 35 He Mia Mc Vw Mur Mg Vr Me Mt aSt Ri aCl Ny Hut Hil Mv Far sD Mit Dantu Hop

Homology Between Genes Creates Diversity

31 2 4 5 6

31 2 4 5 76

t

Low nucleotide identityHigh nucleotide identity

Recombinationhotspot

GYPB

GYPA

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Creation of MNS hybrid genes

GP.SchSt(a+)

GP.Hil (MINY+, Hil+)GP.JL (MINY+, TSEN+)GP.TK (SAT+)

Novel antigens are created at crossover points

GYPA GYPB

GYPB GYPAGYPA GYPB

Unequal crossover

DNA exchange by double strand break repair (DSBR) mechanism leaves one chromosome unaltered

New antigens are encoded by the novel hybrid sequence

GYPA GYPB

GYPB -A -BGYPA

Gene conversion

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GP.HilGenerated by unequal crossover

GP.MurGenerated by gene conversion

GPB

GPB

GPA

Hil

GPB

AHil

GP.Hil GPMurGP.BunGP.HF

Different mechanisms can produce the same antigen

PEEETGETGDL

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MNS Antigens Produced by Hybrids

• Mia, Hut, Mur, MUT, Hil, TSEN, MINY, Hop, Nob, DANE,

Sta, Dantu, SAT

• Antibodies can cause HDN

• The GP.Mur (Mi.III) phenotype is ~15% in Chinese

populations

• HDN due to ”anti-Mia” is a concern

• Anti-Mur +/- MUT

• One of the most common antibodies in Asian populations

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High Prevalence MNS antigens

‘N’

20

24

91

81 ENEV82 ENAV/MARS84 ENEP/HAG

20

68&71 ENKT

150

EnaFR

EnaFS

U

59

48

GPA GPB

Ena

JENU: encoded by GYPB, absent from GP.Mur hybrid

47 ENEH/Vw/Hut

ENDA: encoded by GYPA absent from GP.Dane hybrid

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Null Phenotypes in the MNS System

• En(a−): absence or alteration of GPA

• S−s− : absence or alteration of GPB

• MkMk phenotype: absence of GPA and GPB

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Clinical significance of MNS antibodies

Anti- Ig class HTR HFDN Comments

M IgM/IgG Rarely Rarely Worth monitoring in pregnancy

N IgM>IgG No No

S IgG Yes Yes

s IgG Rarely Rarely

U IgG Yes Yes

Ena IgG Rarely Rarely Can be an autoantibody

’N’ IgG Yes Yes

’Lows’ IgM>IgG No Yes Mabye naturallyoccurring

Many low prevalence MNS antigens have been detected as a consequenceof HDFN in women with negative antibody screens. Disease can range from mild to severe.

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The Kell Blood Group System (ISBT 006)

• 1st antibody – anti-K, identified in 1946 in a report of HDFN

• 36 antigens

• Kell is expressed on:• RBCs, erythropoietic tissues, testes

• Lower expression in brain, lymphoid organs, muscle (heart and skeletal)

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Kell blood group system antigens

001 002 003 004 005 006

K k Kpa Kpb Ku Jsa

007 008 009 010 011 012

Jsb --- --- Ula K11 K12

013 014 015 016 017 018

K13 K14 --- K16 K17 K18

019 020 021 022 023 024

K19 Km Kpc K22 K23 K24

025 026 027 028 029 030

VLAN TOU RAZ VONG KALT KITM

031 032 033 034 035 036

KYO KUCI KANT KASH KELP KETI

037 038 039

KHUL KYOR KEAL Low High

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Geographic variation in expression oflow prevalence antigens

Antigen Ethnic group Occurrence Others

K Whites Arabs

9%25%

<2%

Jsa Blacks (USA) 20% <0.01%

Ula Finns 2.6% <0.01%

Kpc Japanese 0.32% <0.01%

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The KEL gene is located on chromosome 7

Chromosome 7q33 - KEL

19 exons 21,5 kb

exonsintrons

Exons contain coding nucleotides Introns contain non-coding nucleotides:

High percentage of the gene is noncoding but it contains important regulatory sequences

..ccccctctctctcctttaaag CTT GGA GGC TGG CGC ATC

TCT GGT AAA TGG ACT TCC TTA AAC TTT AAC CGA ACG

CTG AGA CTT CTG ATG AGT CAG TAT GGC CAT TTC CCT

TTC TTC AGA GCC TAC CTA GGA CCT CAT CCT GCC TCT

CCA CAC ACA CCA GTC ATC CAG gtgagggatg......

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The Kell glycoprotein

• Type 2 membrane protein732aa; Mr 93 kDa

15 cysteine residues: predicts a heavily folded protein

Glycosylated 5 (4) N-linked branched oligosaccharides

• One of M13 family of neutral zinc endopeptidases

• Specifically cleaves big endothelin-3 to ET-3ET-3 is a powerful vasoconstrictor

• Biological role on RBCs is still unknown

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3

2

1

4

5

6

7

8

9

1012

13

14

15

16

17

18

19

11

KEL

K18+/K18–388C>T; 389G>A

K/k 578T/CK14/K24 538G/C

KTIM+/KYIM– 913G>AK11/K17 905T/CKHUL/KEAL 877C>TKYOR/KYO 875G/AKpb/Kpc 842G/AKpa/Kpb 841T/C KELP+/KELP– 780G>TKASH+/KASH– 758A>GRAZ+/RAZ– 745G>AVLAN–/VLAN+ 743G>AVONG–/VONG+ 742C>T

K13+/K13– 986T>CK22+/K22– 965C>T

K23–/K23+ 1145A>G TOU+/TOU– 1217G>AKUCI+/KUCI– 1271C>TKANT+/KANT– 1283G>T

K19+/K19– 1475G>AUl(a–)/Ul(a+) 1481A>T

K12+/K12– 1523A>G

Reid, Lomas-Francis & Olsson

The blood group antigen factsbook, 3rd ed.

Slide modified from ES Wester et al.

Transfusion 2005,45:545

KELP+/KELP– 2024G>A

Jsa/Jsb 1790C/T

Kell antigens are created by missense SNPs

KETI+/KETI– 1391C>T

KALT+/KALT– 1868G>A

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Kell glycoprotein interacts with XK

COOH

15

NH2

H

E

L

L

H

158

16

3

2

1

4

5

6

7

KEL

17

18

19

9

1012

13

14

11

Exons 1-19

Cys347=Cys72N-glycans

XK

Kell

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Preferential processing of big ET-3 by wild-type s-Kell

Lee S et al. Blood 1999;94:1440-1450

©1999 by American Society of Hematology

S-Kell: His-tagged extracellular domain of Kell gp

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The K0 phenotype

• Null phenotype of the Kell system All Kell antigens are absent

Expression of Kx is elevated

Amount of XK protein is reduced

• No apparent physiological defect

• Reported in all populations

• May produce anti-Ku (KEL5)

• Many molecular backgrounds Missense mutations

Nonsense mutations

Altered splicing due to intron mutations

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Preferential processing of big ET-3 by RBCs of common Kell phenotype: comparison with K0 phenotype

Lee S et al. Blood 1999;94:1440-1450

©1999 by American Society of Hematology

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Reference allele KEL*02 encodes KEL2, KEL4, KEL5, KEL7, KEL11, KEL12, KEL14, KEL18, KEL19, KEL22, KEL26,

KEL27, KEL29, KEL30, KEL32, KEL33, KEL34, KEL35, KEL36, KEL37, KEL38

Phenotype Allele Name Nucleotide change† Intron/

Exon

Amino acid change

K0 KEL*01N.01 c.1678C>G 15 p.Pro560Ala

K0 KEL*01N.02 c.244T>C 4 p.Cys82Arg

K0 KEL*02N.01 c.223+1g>c Intron 3 Alternative splicing:

p.Arg75fs

K0 KEL*02N.02 c.382C>T

c.1790C

4

(17)

p.Arg128Ter

K0 KEL*02N.03 C246T>A 4 p.Cys82Ter

K0 KEL*02N.04 c.1042C>T 9 p.Gln348Ter

K0 KEL*02N.05 c.2027G>A 18 p.Ser676Asn

K0 KEL*02N.06 c.223+1g>a Intron 3 Alternative splicing:

p.Arg75fs

K0 KEL*02N.07 c.574C>T 6 p.Arg192Ter

K0 KEL*02N.08 c.526−2a>g Intron 5 Alternative splicing

Mod phenotypes

Classification of a mod phenotype may depend on the reagents used.

Kmod; KEL:1weak KEL*01M.01 c.578C>G 6 p.Thr193Arg

Kmod KEL*02M.01 c.1088G>A 10 p.Ser363Asn

Kmod KEL*02M.02 c.2030A>G 18 p.Tyr677Cys

Kmod KEL:−13 KEL*02M.03 c.986T>C 9 p.Leu329Pro

Kmod KEL*02M.04 c.2107G>A 19 p.Gly703Arg

Kmod KEL*02M.05 c.1719C>T 16 p.Gly573Gly

Kmod KEL*0M2.06 c.306C>A, c.1298C>T 4, 11 p.Asp102Glu,

p.Pro433Leu

http://www.isbtweb.org/nc/working-parties/red-cell-immunogenetics-and-blood-group-terminology/

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Alloantibodies to Kell Antigens

• Usually IgG1

• Clinically important antibodies: Cause of HTR

Mild to severe HDFN

• Anti-K is the most common alloantibody specificityoutside ABO & Rh systems

• Anti-K often found in sera containing antibodies tohigh incidence Kell antigens

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Anti-K and HDFN

• Kell antigens are well developed on fetal RBCs

• Clinical presentation is very different than HDFN due to other non-Kell antibodies

• Prediction of disease severity based on antibody titre or amniotic bilirubin is unreliable

• Antibodies inhibit erythropoeisis

• Post-delivery: Hyperbilirubinaemia is lower than expected Reduced reticulocytosis Reduced erythroblastosis Very anaemic babies

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Why is the HDFN so severe?

Southcott MJG, et al. The expression of human blood group antigens during erythropoiesis in a cell culture system. Blood 1999;93:4425-35

”… may have an important role in the early stages of hematopoiesis or cell lineage determination.”

Time in culture (days)

Onset of RBC proteins in cultured cord blood

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The Lewis blood group system (ISBT 007)• 6 antigens recognized by ISBT: Lea, Leb, LebH,

ALeb, BLeb, Leab

• Adsorbed onto RBCs from the plasma

• ”Histo-blood” group antigens: Glycoproteins in saliva and blody fluids

Lymphocytes, platelets

Epithelia of various tissues

• Synthesized by α(1,3/4) fucosyltransferaseencoded by FUT3

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Blood group

Le(a+b−)Le(a−b+)Le(a−b−)

RBC Antigens

Lea

Leb

Neither

Secretor?

NoYesYes or No

Lewis antigens and Secretor Status

• FUT2 encodes α2FucT2, which synthesizes H antigen on soluble glycoproteins

Genes

FUT3FUT2, FUT3(FUT2)

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Structure of Lewis Antigens on RBCs

Type 1 chain

Lea and Leb are not synthesized on RBCs, but adsorbed from plasma

Leb

Lea

Rβ1-4β1-3

α1-4

β1-3 β1-1

Rβ1-3β1-3

α1-4α1-2

β1-4 β1-1

R = Core structureGlucose

Fucose

Galactose

GlcNAc

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Function of Lewis Antigens

• Receptors for various pathogens

• Leb identified as the receptor for Helicobacter

pylori

• Sialyl-Lea is a tumour marker

– diagnostic marker in carcinomas such as colorectal,

pancreatic and gastric cancers

• The related sialyl-Lex is not found on RBCs but

expressed on endothelium

– Ligand for selectins

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H. pylori BabA adhesinrecognizes Leb ongastric epitheliumresulting in binding

Mahdavi et al. Science 297:573-578, 2002Slide courtesy of S. Spitalnik

Helicobacter pylori and Gastritis

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Helicobacter pylori and Gastritis

Inflammation increases SLex expression on gastric epithelium,which is recognized by H. pylori SabA adhesin

Mahdavi et al. Science 297:573-578, 2002Slide courtesy of S. Spitalnik

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Helicobacter pylori and Gastritis

Neutrophils, which expresshigh levels of SLex, infiltrateepithelium. Phase variationin H. pylori leads to decreasedSabA expression and evasionof phagocytosis

Mahdavi et al. Science 297:573-578, 2002Slide courtesy of S. Spitalnik

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Antibodies to Lewis antigens

• Mostly IgM

• Oftern naturally occurring

• More often found in plasma from pregnant women

• Readily neutralised by saliva

• Anti-Leb is not clinically significant

• Most anti-Lea are not clinically significant

Blood group

Le(a+b−)Le(a−b+)Le(a−b−)

Anti- Lea

NoVery rarelyOccasionally

Anti- Leb

Very rarelyNoOccasionally

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The Duffy blood group system (ISBT 008)• Consists of 5 antigens:

Polymorphic: Fya, Fyb

High prevalence: Fy3, Fy5, Fy6

• Carried by Atypical Chemokine receptor 1 (ACKR1) on RBCs

• Also found on endothelial cells i capillaries, epithelia of the kidneys, lungs and in brain

(Fya is a high prevalence antigen in South East Asia)

(Fy6 is defined by a monoclonal antibody only)

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N-glycans

Fy3

Fya/Fyb

Fy6

Atypical Chemokine receptor 1 (ACKR1)

RBC membrane

• Major isoform of glycoprotein is 336 aa

• Fya/Fyb at position 42 (Gly42Asp)

• Susceptible to papain/ficin treatment of RBCs

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Genetic basis of Duffy phenotypes

• Polymorphism at −67 (t>c) interrupts a GATA-1 binding site and the gene is not transcribed

• No protein on the RBC

• Fy(a−b−) phenotype Found in >90% West Africans, ~60% of African Americans (FY*B) Also found in Papua New Guinea (FY*A)

Exon 1

−67 265 298

A/GFya/Fyb

C/T”Fyx”

t/c

125

G/A

Exon 2

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Function of ACKR1• Binds different chemokines – RBC chemokine ”sink”

• Associated with hematopoeisis: neutropenia in healthyFy(a−b−) individuals of African ancestry has been associatedwith absence of ACKR1

Nature Immunology 2017

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ACKR1 is a receptor for Plasmodium spp.

• Major receptor for P. vivax and P. knowlesi

• Individuals with Fy(a−b−) phenotype areprotected from infection

• BUT… evidence that ACKR1 protein helps PF4 from platelets kill P. falciparum

Platelet Factor 4 and Duffy Antigen Required for Platelet Killing of Plasmodium falciparum

McMorran et al. Science 2012;338:1348-51.

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McMorran et al. Science 2012;338:1348-51.

Fig. 4

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Antibodies to Duffy blood groupantigens• Readily formed following transfusion

• IgG antibodies

• Anti-Fya and anti-Fyb can cause both transfusion reactions and HDFN

• Anti-Fy3 is generally weak and not clinicallyimportant but… Anti-Fy3 produced by true Fynull individuals (mutations in FY

gene) can be clinically important

• Anti-Fy5 is very rare

• Anti-Fy6 only described as a monoclonal antibodyreactive with a papain-sensitive epitope on ACKR1

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Properties of SLC14A1389 amino acidsMultipass membrane protein

Null phenotypeJk(a−b−)Reduced urine concentrationAnti-Jk3

AntigensJka, Jkb and Jk3

AntibodiesDelayed HTRHDFN

Gene SLC14A1(HUT11A), UT-B Chromosome 18, 10 exons

Jka/Jkb

3

21

5

6

4

7 89

10

11

SLC14A1

Jka/Jkb

3

21

5

6

4

7 89

10

11

SLC14A1

Olives, Lucien, Sidoux-Walter et alInstitute National de la Transfusion Sanguine, Paris

The Kidd blood group system (ISBT 009)

Function

Urea transporterFound on RBCs, kidney, colon

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JK alleles

838G

JK*01

588A

838A

JK*02

588G

-46 a/g

3 st Single Nucleotide Polymorphisms (SNPs)

Asp280Asn

Jka Jkb

Olives et al., J. Biol. Chem. 1994.

Jk(a+)

Jk(b+)

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JK alleles that encode weak antigen expressionReference allele JK*01 encodes JK1, JK3

Phenotype Allele name Nucleotide change Exon Predicted amino acid change

JK:1 or Jk(a+) JK*01 or

JK*A

c.838A>G 8 p.Asn280Asp

JK:2 or Jk(b+) JK*02 or

JK*B

Weak phenotypes

Jk(a+W) JK*01W.01 c.130G>A 3 p.Glu44Lys

Jk(a+W) JK*01W.02 c.511T>C 6 p.Trp171Arg

Jk(a+W) JK*01W.03 c.28G>A 3 p.Val10Met

Jk(a+W) JK*01W.04 c.226G>A 4 p.Val76Ile

Jk(a+W) JK*01W.05 c.742G>A 7 p.Ala248Thr

Jk(b+W) JK*02W.01 c.548C>T 6 p.Ala183Val

Jk(b+W) JK*02W.02 c.718T>A 7 p.Trp240Arg

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The common Jka+w phenotype is due to an intracellular amino acid change

2030

50

60

40

70

100

90

120

130150

170

180

230

240

270

360

80

110

140

160

190

200

210

220

370

380

Asp280Asn

Jka/Jkb

340

350

300

290

310

320

330

Glu44Lys

Pro196

10

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Function of Jk (SLC14A1)

• Major urea transporter on RBCs and kidneys

• Absence of SLC14A1 has no clinical symptoms but individuals have reduced urine concentratingability

• Since SLC14A1 is an important functional protein in kidneys, Jka/Jkb are minor histocompatibilityantigens in transplantation

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The Jk(a−b−) phenotype

• Rare phenotype but up to 1% in Polynesians

• RBCs are resistant to hemolysis by 2M Urea

Phenotype Urea transport Hemolysis

Jknull Passive 30 min

Jka/Jkb Passive/Active 1 min

Jk(a+b-) Jk(a-b-) Jk(a-b-)

Read after 2 min

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JK alleles that silence antigen expressionNull phenotypes JK*02

JK:–3 or Jk(a–b–) JK*02N.01 c.342-1G>A Intron 4 p.Arg114_Thr156del; Alternative

splicing

JK:–3 or Jk(a–b–) JK*02N.02 c.342-1G>C Intron 4 p.Arg114_Thr156del; Alternative

splicing

JK:–3 or Jk(a–b–) JK*02N.03 c.222C>A 4 p.Asn74Lys

JK:–3 or Jk(a–b–) JK*02N.04 c.663+1G>T Intron 6 p.Leu223fs*?; Alternative splicing

JK:–3 or Jk(a–b–) JK*02N.05 c.723delA 7 p.Gly243Alafs*20

Identical to JK*01N07? (c.838A>G is

located past termination)

JK:–3 or Jk(a–b–) JK*02N.06 c.871T>C 8 p.Ser291Pro

JK:–3 or Jk(a–b–) JK*02N.07 c.896G>A 8 p.Gly299Glu

JK:–3 or Jk(a–b–) JK*02N.08 c.956C>T 9 p.Thr319Met

JK:–3 or Jk(a–b–) JK*02N.09 c.191G>A 4 p.Arg64Gln

JK:–3 or Jk(a–b–) JK*02N.10 c.194G>A 4 p.Gly65Asp

JK:–3 or Jk(a–b–) JK*02N.11 c.499A>G; c.512G>A 6 p.Met167Val; p.Trp171Ter

JK:–3 or Jk(a–b–) JK*02N.12 c.437T>C; c.499A>G 5; 6 p.Leu146Pro; p.Met167Val

JK:–3 or Jk(a–b–) JK*02N.13 c.499A>G; c.536C>G 6 p.Met167Val; p.Pro179Arg

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Antibodies to Kidd blood groupantigens

• Readily formed following transfusion

• IgG antibodies

• Anti-Jka, -Jkb and anti-Jk3 can cause severehemolytic immediate/delayed transfusion reactions

• HDFN is mild to moderate

• Anti-Jka and anti-Jkb may disappear rapidly butare readily boosted by transfusion of antigen-positive blood

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For more information on blood group alleles….

www.erythrogene.com

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Thank you for yourattention!

Questions?

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Questions?

• You are all muted

• Q&A following session - Type in questions

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Questions?

• You are all muted

• Q&A following session - Type in questions

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Continuing Education

• PACE, Florida and California DHS

• 1.0 Contact Hours

• Each attendee must register to receive CE at: https://www.surveymonkey.com/r/TheJollyBloodBanker

• Registration deadline is April 5, 2019

• Certificates will be sent via email only to those

who have registered April 19, 2019

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