A variant of SCID with specific immune responses and predominance of gamma delta T cells

J Clin Invest. 2005 Nov;115(11):3140-8. doi: 10.1172/JCI25221. Epub 2005 Oct 6.

Abstract

We describe here a patient with a clinical and molecular diagnosis of recombinase activating gene 1-deficient (RAG1-deficient) SCID, who produced specific antibodies despite minimal B cell numbers. Memory B cells were detected and antibodies were produced not only against some vaccines and infections, but also against autoantigens. The patient had severely reduced levels of oligoclonal T cells expressing the alphabeta TCR but surprisingly normal numbers of T cells expressing the gammadelta TCR. Analysis at a clonal level and TCR complementarity-determining region-3 spectratyping for gammadelta T cells revealed a diversified oligoclonal repertoire with predominance of cells expressing a gamma4-delta3 TCR. Several gammadelta T cell clones displayed reactivity against CMV-infected cells. These observations are compatible with 2 non-mutually exclusive explanations for the gammadelta T cell predominance: a developmental advantage and infection-triggered, antigen-driven peripheral expansion. The patient carried the homozygous hypomorphic R561H RAG1 mutation leading to reduced V(D)J recombination but lacked all clinical features characteristic of Omenn syndrome. This report describes a new phenotype of RAG deficiency and shows that the ability to form specific antibodies does not exclude the diagnosis of SCID.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cells, Cultured
  • Clone Cells
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / immunology
  • Female
  • Fibroblasts / immunology
  • Fibroblasts / virology
  • Homeodomain Proteins / genetics
  • Humans
  • Immunophenotyping
  • Infant
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell, gamma-delta / analysis
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Severe Combined Immunodeficiency / genetics
  • Severe Combined Immunodeficiency / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • Homeodomain Proteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • RAG-1 protein