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Disturbed B and T cell homeostasis and neogenesis in patients with ataxia telangiectasia

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Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

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.

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).

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.

Conclusion

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.

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Abbreviations

AT:

Ataxia telangiectasia

ATM:

AT mutated

BCR:

B-cell receptor

CJ:

Coding joints

CPM:

Counts per minutes

IGH:

Immunoglobulin heavy chain

IVIG:

Intravenous immunoglobulin

KREC:

Kappa-deleting recombination excision circles

ND:

Not done

PMBC:

Peripheral blood mononuclear cell

RQ-PCR:

Real-time quantitative polymerase chain reaction

SJ:

Signal joints

TCR:

T-cell receptor

TREC:

T-cell receptor excision circle

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Acknowledgments

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.

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Authors and Affiliations

  1. Pediatric Immunology Unit, Jeffrey Modell Foundation (JMF) Center and Department of Pediatrics, Sheba Medical Center, Tel Hashomer, Israel

    Matan Kraus, Atar Lev & Amos J. Simon

  2. Pediatric Department, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Israel

    Inbal Levran

  3. Pediatric Neurology Unit, Ataxia Telangiectasia National Clinic, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Israel

    Andrea Nissenkorn

  4. Ataxia Telangiectasia National Clinic, Edmond and Lily Children’s Hospital, Sheba Medical Center, Tel Hashomer, Israel

    Yonit B. Levi

  5. Ataxia Telangiectasia National Clinic, Hadassah-Hebrew University Medical Centerr, Mount Scopus Jerusalem, Israel

    Yackov Berkun

  6. Pediatric Pulmonary Unit, Ataxia Telangiectasia National Clinic, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Israel

    Ori Efrati

  7. Cancer Research Center, Sheba Medical center, Tel Hashomer, Israel

    Ninette Amariglio & Gideon Rechavi

  8. Cancer Research Center, Pediatric Immunology Unit, Jeffrey Modell Foundation (JMF) Center, Department of Pediatrics, Ataxia Telangiectasia National Clinic, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, affiliated with the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Raz Somech

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  1. Matan Kraus
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  2. Atar Lev
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  3. Amos J. Simon
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  4. Inbal Levran
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  5. Andrea Nissenkorn
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  6. Yonit B. Levi
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  7. Yackov Berkun
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  8. Ori Efrati
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  9. Ninette Amariglio
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  10. Gideon Rechavi
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  11. Raz Somech
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Corresponding author

Correspondence to Raz Somech.

Additional information

Matan Kraus and Atar Lev contributed equally

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Kraus, M., Lev, A., Simon, A.J. et al. Disturbed B and T cell homeostasis and neogenesis in patients with ataxia telangiectasia. J Clin Immunol 34, 561–572 (2014). https://doi.org/10.1007/s10875-014-0044-1

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  • DOI: https://doi.org/10.1007/s10875-014-0044-1

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