J ALLERGY CLIN IMMUNOL

VOLUME 125, NUMBER 2

Abstracts AB73

SU

ND

AY

286 Evolutive Profile Of Iga Deficiency Patients From A PediatricBrazilian Reference Center For Primary Immunodeficiency

M. B. Dorna, M. T. Iwashita, D. G. C. Rezende, L. A. Watanabe, M. D.

Asanuma, A. C. Pastorino, A. P. B. M. Castro, A. B. F. Fomin, M. M. S.

Carneiro-Sampaio, C. M. A. Jacob; Allergy and Immunology Unit -

Child’s Institute - Pediatric Department - Faculdade de Medicina da Uni-

versidade de Sao Paulo, Sao Paulo, BRAZIL.

RATIONALE: To describe the clinical features of IgA deficiency (IgAD)

patients followed at a pediatric Brazilian reference center for primary im-

munodeficiency (PID).

METHODS: Retrospective study from 81 patients (1,02M: 1F) diagnosed

with IgAD (IUIS criteria) and followed at Allergy and Immunology Unit -

Faculdade de Medicina - Universidade de Sao Paulo in the last 27 years.

Clinical features and laboratorial data were evaluated.

RESULTS: Median time of follow-up was 6,2y. Age at the diagnosis var-

ied from 4 to 18,7 years (median 5 6,8y). Concerning the reasons for in-

vestigating IgAD it was found: recurrent infections in 55,5%, allergic

diseases in 14,8%, autoimmunity in 8,6%, severe or complicated infections

in 7,4% and familial history of IgAD in 5% of patients. Infections detected

during follow up were: upper respiratory tract infection (76,5%, 1-37 epi-

sodes/patient), pneumonia (60,5%), skin and subcutaneous infection

(19,9%) and other infections in 14,8%. Giardiasis was diagnosed in

18,5% patients, followed by ascaridiase in 7,4%. Allergic diseases were

observed 75,3%, and auto-immunity in 13,5%. Eleven patients referred

at least one family member with IgAD (nine different families) and 6, fa-

milial history for auto-immunity. One mother’s patient had CVID.

Regarding the laboratorial evolution, 4 patients presented normalization

of the IgA levels (median age 18,1y) and 14 showed elevation of IgA levels

(IgA>7mg/dl but <p3 for the age). One patient developed CVID at the age

of 12,7y.

CONCLUSION: Patients with IgA deficiency demand long term follow-

up due to the possibility of various clinical and laboratorial evolutions with

different degrees of immunological impairment and the development of

autoimmunity.

287 A Novel Mutation in STAT3 in a Family with AutosomalDominant Hyper-IgE Syndrome

A. Kovalszki1, A. P. Hsu2, S. M. Holland2, A. P. Baptist3; 1Beth Israel

Deaconess Medical Center, Harvard Medical School, Boston, MA, 2Lab-

oratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD,3University of Michigan, Ann Arbor, MI.

RATIONALE: To identify the molecular basis of disease in a family pre-

senting with increased susceptibility to infections.

METHODS: Extended family history was obtained in a 31-year-old fe-

male, her 5-year-old son, and her 53-year-old mother presenting with a his-

tory of increased infections. Blood was sent for routine immunologic

evaluations including quantitative immunoglobulins, complete blood

count, and neutrophil oxidative burst. Blood samples obtained from the

son, mother and grandmother, were analyzed for STAT3 mutations by

cDNA sequencing.

RESULTS: History was remarkable for staphylococcal skin, bone and

blood infections, retained primary teeth, scoliosis, hyperextensibility, fun-

gal skin infections and eczema. Most infections occurred in the mother

when she was young, improving with age. Extended family history was

positive for multiple family members being affected by lung, skin, and

other infections, spanning four generations. Immunologic workup was un-

remarkable except for slightly elevated IgE levels (2296, 682 and 663 IU/

mL in grandmother, mother, and son). Facial morphometric features of hy-

per-IgE syndrome were not apparent. Sequencing of STAT3 cDNA re-

vealed a novel heterozygous mutation, c1003C>T, in a highly conserved

and exposed region of the DNA binding domain resulting in arginine to

tryptophan substitution at amino acid position 335 in three generations.

CONCLUSIONS: R335W STAT3 mutation was associated with a pheno-

typically distinct variant of hyper-IgE syndrome with less coarse facial

features, milder IgE elevations, and a milder presentation of immunodefi-

ciency primarily in childhood in the family members evaluated in this

study. However, variability in clinical severity among extended family

members suggests presence of other modifying factors in addition to the

STAT3 mutation.

288 Progression of Specific Antibody Deficiency (SAD) toCommon Variable Immunodeficiency (CVID)

S. P. Wilson, Z. K. Ballas; VA Medical Center and University of Iowa

Hospitals & Clinics, Department of Internal Medicine, Iowa City, IA.

RATIONALE: SAD and CVID are common types of humoral immune de-

ficiency. This study was undertaken to test the hypothesis that SAD repre-

sents an early form of CVID and that, over time, SAD might evolve to

CVID.

METHODS: A retrospective chart review was undertaken on patients seen

in the University of Iowa Hospitals & Clinics adult immune disorder clinic.

Records of patients with a CVID diagnosis were examined for prior eval-

uation of SAD. SAD was defined as a suboptimal response to pneumococ-

cal vaccination.

RESULTS: We found 6 patients who initially were diagnosed with SAD

who later acquired decreased IgG, and decreased IgA or IgM. The mean

age of presentation was 43. The mean time to progression from SAD to

CVID was 54 months, and the median was 57 months, with a range of 8

to 185 months. Presenting symptoms included bronchiectasis, septic arthri-

tis with Mycoplasma pneumoniae and Mycobacterium avium intracellu-

lare osteomyelitis/diskitis, pharyngitis and wound infection, and sino-

pulmonary infections. 5 patients had IgG subclasses checked at the time

of SAD diagnosis; of these 1 patient had decreased IgG1, and 2 patients

had decreased IgG2.

CONCLUSIONS: These patients suggest that SAD might be an early

manifestation of CVID. We were not able to identify any characteristics

that would allow prediction as to who will develop CVID.

289 Outcome of using PET Imaging as a Diagnostic Tool for TwoPatients with Common Variable Immunodeficiency (CVID) andLymphadenopathy

M. Michelis, J. Hirsch, S. McGuirt, B. McGoey; Hackensack University

Medical Center, Hackensack, NJ.

RATIONALE: Lymphoid hyperplasia, along with a high risk of lym-

phoma has been reported in CVID patients. PET imaging has been used

to differentiate malignant from nonmalignant lymphoid proliferation.

METHODS: Chart review of 2 CVID patients with abnormal PET

imaging.

RESULTS: Patient A: 54-year-old male diagnosed with CVID had a body

CT that revealed diffused lymphadenopathy, as well as pulmonary nodules.

Follow-up PET imaging revealed extensive chest lymphadenopathy with

the greatest uptake in right paratracheal region and left pleural based nod-

ule. Image-guided needle biopsy revealed a polyclonal B-cell population.

Subsequent lung wedge and hilar lymph node biopsy revealed no evidence

of lymphoma. Patient B: 41-year-old-male diagnosed with CVID under-

went a CT angiogram of the abdomen that revealed extensive axillary

and mesenteric lymphadenopathy. PET imaging revealed multiple abnor-

mal foci of hypermetabolism, corresponding to bilateral axillary and

abdominal adenopathy. A fine needle aspirate of the right axillary lymph

node revealed increased reactive lymphoid T cells. Subsequent PET

Imaging revealed increase in abnormal foci as well as multiple new foci

within the spleen. An excisional biopsy of the right axillary lymph node

revealed features suggestive of Hodgkin’s lymphoma.

CONCLUSION: These two cases exemplify the limited value of PET

Imaging in distinguishing lymphoma from atypical lymphadenopathy in

patients with CVID and that excisional biopsies should be done with per-

sistently positive PET imaging. These clinical findings also underscore the

need to wait 2 years before diagnosing CVID in a patients presenting with

hypogammaglobulinemia.