Thymic function in MHC class II-deficient patients

Atar Lev, Amos J. Simon, Arnon Broides, Jacob Levi, Ben Zion Garty, Ester Rosenthal, Ninette Amariglio, Gideon Rechavi, Raz Somech

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Background: MHC class II (MHC-II) molecules play a pivotal role in the development, activation, and homeostasis of CD4+ TH cells in the thymus. The absence of MHC-II molecules causes severe T-cell immunodeficiency. Objective: We sought to study thymic function, including T-cell receptor excision circle (TREC) quantification, in patients with MHC-II deficiency. Methods: Eight MHC-II-deficient patients underwent a thorough T-cell immunologic work-up, including thymic activity, which was estimated based on TREC levels and T-cell receptor (TCR) genes, as well as analysis of several sequential human TCR gene rearrangements. Results: In vitro responses to mitogens were normal or only slightly reduced, and flow cytometric evaluations of the TCR-Vβ repertoires of total CD3+ lymphocytes were normal in all patients. However, both the flow cytometric evaluation of the TCR-Vβ repertoire on CD4+ cells and spectratyping evaluation of the TCR-Vγ repertoire on total CD3+ lymphocytes showed clonal abnormalities. TRECs were present in all patients in both total lymphocytes and sorted CD4+ cells. Additionally, TRECs were detected in genomic DNA obtained from Guthrie cards with dried blood spots. Quantitative RT-PCR assessment of different TCR gene rearrangement events revealed lower levels in MHC-II-deficient patients compared with levels seen in healthy control subjects. This was irrespective of the total lymphocyte numbers, suggesting a reduced global thymic activity. Conclusions: Our report highlights potential pitfalls in diagnosing MHC-II deficiency and emphasizes the probable importance of MHC-II molecules in the normal thymic maturation process of T cells. Patients with MHC-II deficiency have detectable TRECs and might therefore be missed by a TREC-based newborn screening program.

Original languageEnglish
Pages (from-to)831-839
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume131
Issue number3
DOIs
StatePublished - Mar 2013
Externally publishedYes

Bibliographical note

Funding Information:
Supported by the Jeffery 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 (to R.S.)

Funding Information:
Disclosure of potential conflict of interest: R. Somech has received research support from the Legacy Heritage Biomedical Science Partnership Program of the Israel Science Foundation and the Chief Scientist Office of the Ministry of Health. The rest of the authors declare that they have no relevant conflicts of interest.

Keywords

  • MHC class II
  • T-cell receptor excision circle (TREC)
  • T-cell receptor repertoire
  • immunodeficiency
  • neonatal screening
  • severe combined immunodeficiency

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