Multiple reversions of an IL2RG mutation restore T cell function in an X-linked severe combined immunodeficiency patient

J Clin Immunol. 2012 Aug;32(4):690-7. doi: 10.1007/s10875-012-9684-1. Epub 2012 Mar 30.

Abstract

Reversion mosaicism is increasingly being reported in primary immunodeficiency diseases, but there have been few cases with clinically improved immune function. Here, a case is reported of X-linked severe combined immunodeficiency (SCID-X1) with multiple somatic reversions in T cells, which restored sufficient cell-mediated immunity to overcome viral infection. Lineage-specific analysis revealed multiple reversions in T cell receptor (TCR) αβ+ and TCRγδ+ T cells. Diversity of the TCRVβ repertoire was comparable to normal and, furthermore, mitogen-induced proliferation of the patient's T cells was minimally impaired compared to healthy controls. In vivo and in vitro varicella antigen-specific T cell responses were comparable to those of healthy controls, although a reduced level of T cell receptor excision circles suggested that recent thymic output was low. During long-term evaluation of the patient's immunologic status, both the number of CD4+ and CD8+ T cells and T cell proliferation responses were stable and the patient remained healthy. This case demonstrates that multiple but restricted somatic reversions in T cell progenitors can improve the clinical phenotype of SCID-X1.

Publication types

  • Case Reports

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Child
  • Humans
  • Immunity, Cellular
  • Interleukin Receptor Common gamma Subunit / genetics*
  • Lymphocyte Activation
  • Male
  • Mutation
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • T-Lymphocytes / immunology*
  • X-Linked Combined Immunodeficiency Diseases / genetics*
  • X-Linked Combined Immunodeficiency Diseases / immunology*

Substances

  • IL2RG protein, human
  • Interleukin Receptor Common gamma Subunit
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta