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

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 up TCR but surprisingly normal numbers of T cells expressing the gamma delta TCR. Analysis at a clonal level and TCR complementarity-determining region-3 spectratyping for gamma delta T cells revealed a diversified oligoclonal repertoire with predominance of cells expressing a gamma 4-delta 3 TCR. Several gamma delta T cell clones displayed reactivity against CMV-infected cells. These observations are compatible with 2 non-mutually exclusive explanations for the gamma delta 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.