J ALLERGY CLIN IMMUNOL

VOLUME 127, NUMBER 2

Abstracts AB89

SUNDAY

331 Idiopathic CD41 Lymphocytopenia: Clinical and AutoimmunePhenotype

J. W. Leiding1, J. Heimall2, Y. Song3, S. M. Holland1, R. M. Siegel3, A. F.

Freeman1; 1National Institute of Allergic and Infectious Diseases, Be-

thesda, MD, 2The Children’s Hospital of Philadelphia, Philadelphia, PA,3National Institute of Arthritis and Musculoskeletal and Skin Diseases,

Bethesda, MD.

RATIONALE: Idiopathic CD41 lymphocytopenia (ICL) typically

presents in adulthood and may be associated with autoimmunity.

Abnormal T cell apoptosis has been hypothesized as a cause of ICL. We

characterized ICL clinical and immunologic features and the effect of

IL-7 on ICL T cell survival.

METHODS: ICL was diagnosed using standard CDC criteria.

Lymphocyte phenotyping, autoantibodies, and rheumatologic examina-

tions were done. PBMC’s were cultured with IL-7 for 4 days and CD41cells enumerated on days 0, 2, and 4.

RESULTS: Twenty-two patients were evaluated. Fourteen had opportun-

istic infections: disseminated Cryptococcus(5), widespread HPV1 warts

(5), histoplasmosis(2), and Mycobacterium avium complex(2). Six

patients had isolated CD41 lymphopenia, 3 with autoimmunity. Sixteen

patients had CD41 and CD81 lymphopenia, 9 with autoimmunity; 4

had autoantibodies without disease. Nine patients had low NK counts; 4

low B cell counts. Frequency of na€ıve T cells (CD41CD45RA1%) was

disproportionately decreased compared to normal control range in 13/17

patients. Autoantibodies present were: ANA(7), lupus anticoagulant(5),

anticardiolipin(4), dsDNA(3), anti-thyroperoxidase(3), anti-thyroglobu-

lin(2), anti-thyrotropin receptor(1), anti-ENA(1), pANCA(1), anti-RNP

(1), anti-SSA(1), anti-myeloperoxidase(1), and anti intrinsic factor anti-

bodies(1). Seven patient samples, 4 with autoimmunity and 3 without,

stimulated with IL-7 showed no difference in CD41 survival.

CONCLUSIONS: Fungal disease and persistent warts are common pre-

sentations of ICL. Decreased na€ıve CD41 populations suggest a produc-

tion defect in ICL. IL-7 did not affect T cell survival in vitro suggesting

that defects in IL-7 mediated apoptosis rescue are unlikely.

Autoantibodies are common, especially in patients with concurrent

CD81 lymphopenia. Adult onset of disease and autoantibodies suggest au-

toimmunity is a common aspect of ICL.

332 Novel Mutation in Syntaxin-Binding Protein 2 (STXBP2) inFamilial Hemophagocytic Lymphohistiocytosis Type 5 (FHL-5)Prevents IL-2-induced Natural Killer Cell Cytotoxicity andDegranulation

R. W. Saltzman1, L. Monaco-Shawver2, K. E. Sullivan1, J. S. Orange1;1The Children’s Hospital of Philadelphia, Philadelphia, PA, 2The Chil-

dren’s Hospital of Philadelphia Research Institute, Philadelphia, PA.

RATIONALE: Familial Hemophagocytic Lymphohistiocytosis (FHL) is

an autosomal recessive primary immunodeficiency characterized by mul-

tisystem inflammation after infection. In a subset of patients (FHL-5) dis-

ease results from mutation of Munc18-2, which encodes for syntaxin-

binding protein 2 (STXBP2). STXBP2 interacts with syntaxin 11, a

SNARE protein, and controls vesicle fusion with the plasma membrane.

In these patients, natural killer (NK) cell degranulation and cytotoxicity

is impaired, but can be restored after IL-2 stimulation, suggesting an

STXBP2-independent pathway to access SNARE function.

METHODS: Patients suspected for FHL were assessed according to pub-

lished criteria and known genes underlying the disorder sequenced. NK

cells were evaluated for cytotoxic activity and IL-2-induced function.

RESULTS: 19 month old dizygotic twins were identified with novel bial-

lelic mutations for Munc18-2 [474_483 del_insGA/1001 C>T (P334L)].

The index patient presented with fulminant Ebstein-Barr virus and fulfilled

all HLH diagnostic criteria. His twin brother has remained asymptomatic.

IL-2 stimulation of NK cells from either child failed to restore cytotoxicity.

CONCLUSIONS: These FLH-5 patients are the first reported to have a

fixed deficiency of NK cell degranulation. Thus it is unlikely that IL-2 is

inducing a pathway to cytotoxicity truly independent of STXPB2.

Enthusiasm for treating this disorder with IL-2 should be tempered and

at least consider the results of direct in vitro testing before consideration.

333 Clinical Conditions Associated with PCP in ChildrenS. Albin, R. W. Saltzman, P. Russo, K. E. Sullivan; Children’s

Hospital of Philadelphia, Philadelphia, PA.

RATIONALE: Pneumocystis jirovecii is a leading cause of opportunistic

infections among the immune compromised. During the 1980s, attention

shifted to those patients with HIV, however, with the advent of highly

active anti-retroviral therapy and more comprehensive chemoprophylaxis

for Pneumocystis, we wished to revisit the question of underlying diseases

associated with Pneumocystis in children.

METHODS:We identified 82 children with silver stain positive bronchoal-

veolar lavage specimens or lung biopsy specimens at our institution between

1986-2006. We then performed a retrospective chart review to identify clin-

ical characteristics and underlying conditions for each of the cases. A struc-

tured case report form was used to collect data. Of the 82 pathology

specimens, 69 had sufficient clinical data recorded tobe included in the study.

RESULTS: Pneumocystis associated with HIV had the poorest outcome,

however, clinical features were not markedly different between cases

with HIV, malignancy, transplantation, primary immune deficiency or

other conditions. Among the group without known high risk conditions,

steroid use and several diseases not know to be associated with

Pneumocystis were identified.

CONCLUSIONS: HIV was still the single most commonly associated un-

derlying condition seen in this cohort of children with PCP. Notably, it com-

prised only 36%of the cases overall, demonstrating that the epidemiology of

Pneumocystis now encompasses far more disease states and iatrogenic

causes than in the late 1990s. This study documents the ongoingneed for vig-

ilance to diagnose Pneumocystis in less well-recognized clinical scenarios.

334 Primary Immunodeficiencies in Brazilian patients youngerthan five years old

M. B. Dorna1, L. A. Watanabe1, A. B. F. Fomin1, A. C. Pastorino1,

C. M. A. Jacob1, C. A. A. Silva1, D. M. Vasconcelos2, M. M. S. Car-

neiro-Sampaio1; 1DEPT. OF PEDIATRICS, Faculdade de Medicina da

Universidade de S~ao Paulo, S~ao Paulo, BRAZIL, 2DEPT. OF DERMA-

TOLOGY, Faculdade de Medicina da Universidade de S~ao Paulo, S~ao

Paulo, BRAZIL.

RATIONALE: Primary Immunodeficiencies (PID) represent a heteroge-

neous group of diseases whose prognosis depends on early diagnosis and

treatment. Inmost PID series so far reported, the distribution for age groups

in the first years of life has not been emphasized. The aim of this study was

to describe the experience of a pediatric Brazilian reference center for PID

in children younger than 5 years.

METHODS: Evaluation of 251 patients with well characterized PID

distributed into the eight PID groups according to the latest IUIS classifi-

cation (2009). Patients were allocated into 2 age groups: Group 1 (<2

years-old) and Group 2 (2-5 years-old).

RESULTS: In Group 1 (n5118, 74% males), combined T and B-cell im-

munodeficiencies were the most frequent type (25%), followed by phago-

cyte defects (21%), antibody deficiencies (16%), diseases of immune

dysregulation (14%), other well-defined immunodeficiency syndromes

(13%), being the groups of autoinflammatory syndromes (5%), innate im-

munity deficiencies (2%), and complement deficiencies (4%) the less com-

mon. The analysis of Group 2 (n5133, 67%males) demonstrated antibody

deficiencies as the predominant group (44%), followed by well-defined

syndromes (17%), phagocyte defects (15%), complement deficiencies

(9%), diseases of immune dysregulation (8%), combined T and B-cell

deficiencies (4%), innate immunity deficiencies (2%) and autoinflamma-

tory syndromes (1%). The authors point out the predominance of severe

combined immunodeficiencies among the infants.

CONCLUSION:The knowledge of the unique PID distribution in specific

age groupsmay allow development of surveillance programs aswell as ear-

lier detection, leading to more efficacious treatment and better prognosis.