Disturbed B and T cell homeostasis and neogenesis in patients with ataxia telangiectasia.
OBJECTIVE
Ataxia telangiectasia (AT) is a rare genetic, multi-system disorder characterized by neurodegeneration, chromosome instability, B and T cell immunodeficiency and a predisposition to cancer. We examined immunologic parameters reflecting cell development and proliferation and their relevancy to the clinical phenotype in affected individuals.


METHODS
AT patients from the AT National Clinic in Israel underwent immunological investigation. Their T and B cell workup included lymphocyte subset counts, immunoglobulin levels, responses to mitogenic stimulations, TCR-Vβ families and BCR immunoglobulin heavy chain spectratyping, TCR rearrangement excision circles (TRECs) and Kappa-deleting recombination excision circles (KRECs).


RESULTS
Thirty-seven AT patients (median age 12.7 years, range 4.2-25.1) were evaluated. CD20 B and CD3 T lymphocytes were decreased in 67 % and 64 % of the patients, respectively, while only 33 % of the patients had reduced lymphoproliferative responses. Almost all AT patients displayed extremely low TRECs and KRECs levels, irrespective of their age. Those levels were correlated to one another and to the amounts of CD3+ and CD20+ cells, respectively. Abnormal TCR-Vβ repertoires were found with different degrees of clonality or reduced expression in these AT patients. There was no clear clustering of expansions to specific TCR-Vβ genes. PCR spectratyping analysis of the FR2 IgH BCR gene rearrangements in peripheral blood was abnormal in 50 % of the patients.


CONCLUSIONS
The immunodeficiency associated with AT is combined, remains low over time and not progressive. It is characterized by low TREC and KREC copies suggestive of abnormal T and B cell neogenesis.
Pediatric Immunology Unit, Jeffrey Modell Foundation (JMF) Center and Department of Pediatrics, Sheba Medical Center, Tel Hashomer, Israel.
Matan
M
Kraus
Atar
A
Lev
Amos J
AJ
Simon
Inbal
I
Levran
Andrea
A
Nissenkorn
Yonit B
YB
Levi
Yackov
Y
Berkun
Ori
O
Efrati
Ninette
N
Amariglio
Gideon
G
Rechavi
Raz
R
Somech
D000293:Adolescent; D000328:Adult; D018951:Antigens, CD20 / Q000235:genetics / Q000276:immunology; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007159:Immunologic Tests; D016130:Immunophenotyping; D008297:Male; D009154:Mutation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
D018951:Antigens, CD20; D017252:CD3 Complex; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins