Reduced central tolerance in Omenn syndrome leads to immature self-reactive oligoclonal T cells

Raz Somech*, Amos J. Simon, Atar Lev, Ilan Dalal, Zvi Spirer, Itamar Goldstein, Meital Nagar, Ninette Amariglio, Gideon Rechavi, Chaim M. Roifman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Background: Omenn syndrome (OS) is characterized by a peculiar severe T-cell immune deficiency associated with autoimmunelike manifestations. Dysregulations of the central and peripheral immune tolerance, mediated by the protein autoimmune regulator (AIRE) and regulatory T cells, respectively, were proposed as possible mechanisms of this aberrant inflammatory process. Objective: We studied mechanisms of central and peripheral tolerance in patients with OS and also examined the gene expression profile associated with OS features. Methods: T-cell receptor diversity, DNA rearrangement, and the expression of AIRE and forkhead box P3 mRNA as well as the expression of regulatory T cells in cells obtained from patients with OS were studied. Characterization of gene expression in these cells was carried out by using the TaqMan Low-Density Array. Results: Transcript expression of peripheral blood AIRE but not forkhead box P3 was reduced in patients with OS. The expression of natural killer T and regulatory T cells was normal, although the latter showed an abnormal CD4-negative population. Patients with OS have oligoclonal T cells with limited DNA recombination activity, including the presence of early but not late T-cell maturation events, regardless of the genetic defect underlying the syndrome. The transcriptional profile associated with OS features reveals significant changes in 25.5% of the tested genes compared with normal control. Conclusion: Our findings suggest that T-cell oligoclonal expansion in OS emanates from an incomplete block before the maturation stage of negative selection, which may explain escape of autoreactive T cells from the thymus. Dysregulated genes in patients with OS are closely involved with self-tolerance and autoimmunity.

Original languageEnglish
Pages (from-to)793-800
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Issue number4
StatePublished - Oct 2009
Externally publishedYes


  • AIRE
  • Foxp3
  • Omenn syndrome
  • SCID
  • TREC
  • Treg
  • autoimmunity
  • immunodeficiency
  • oligoclones
  • tolerance


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