Disturbed B and T cell homeostasis and neogenesis in patients with ataxia telangiectasia
- 463 Downloads
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.
Patients and 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).
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.
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.
KeywordsAtaxia telangiectasia ATM Combined immunodeficiency Kappa-deleting recombination excision circles KREC T cell recombination excision circles TREC
Counts per minutes
Immunoglobulin heavy chain
Kappa-deleting recombination excision circles
Peripheral blood mononuclear cell
Real-time quantitative polymerase chain reaction
T-cell receptor excision circle
The Jeffrey Modell Foundation (JMF), the Legacy Heritage Biomedical Science Partnership Program of the Israel Science Foundation and the Chief Scientist Office of the Ministry of Health for their support of Dr. Somech. Esther Eshkol is thanked for editorial assistance. This work was performed in partial fulfillment of the M.D. thesis requirements of the Sackler Faculty of Medicine, Tel Aviv University (M.K.).
The authors have no financial relationships relevant to this article to disclose.
The authors have no conflicts of interest relevant to this article to disclose.
- 12.Shearer WT, Rosenblatt HM, Gelman RS, Oyomopito R, Plaeger S, Stiehm ER, et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. The Journal of allergy and clinical immunology. 2003;112(5):973–80. Epub 2003/11/12.PubMedCrossRefGoogle Scholar
- 14.van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17(12):2257–317. Epub 2003/12/13.PubMedCrossRefGoogle Scholar
- 22.Driessen GJ, Ijspeert H, Weemaes CM, Haraldsson A, Trip M, Warris A, et al. Antibody deficiency in patients with ataxia telangiectasia is caused by disturbed B- and T-cell homeostasis and reduced immune repertoire diversity. The Journal of allergy and clinical immunology. 2013;131 (5):1367–75 e9. Epub 2013/04/10.Google Scholar