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

Stephan Ehl*, Klaus Schwarz, Anselm Enders, Ulrich Duffner, Ulrich Pannicke, Joachim Kühr, Françoise Mascart, Annette Schmitt-Graeff, Charlotte Niemeyer, Paul Fisch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

135 Citations (Scopus)

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 αβ TCR but surprisingly normal numbers of T cells expressing the γδ TCR, Analysis at a clonal level and TCR complementarity-determining region-3 spectratyping for γδ T cells revealed a diversified oligoclonal repertoire with predominance of cells expressing a γ4-δ3 TCR. Several γδ T cell clones displayed reactivity against CMV-infected cells. These observations are compatible with 2 non-mutually exclusive explanations for the γδ 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.

Original languageEnglish
Pages (from-to)3140-3148
Number of pages9
JournalJournal of Clinical Investigation
Volume115
Issue number11
DOIs
Publication statusPublished - Nov 2005
Externally publishedYes

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