Immunopathology & Immunotherapy

Lymphocyte receptor diversity is generated by recombining variable, diversity, and joining (VDJ) gene segments of the immunoglobulin and T-cell receptor (TCR) loci. V(D)J recombination requires DNA breakage, a process mediated by recombination-activating gene (RAG) 1 and 2. RAG deficiency was initially described in patients with the T−B− severe combined immunodeficiency (SCID) phenotype1; however, the spectrum of the disease has expanded to include Omenn syndrome, cytomegalovirus infection with γδ T-cell expansion, combined immunodeficiency with granuloma, and isolated CD4+ lymphopenia.2, 3, 4, 5, 6 The pleomorphic manifestations of RAG deficiency are partially explained by residual RAG activity, with null mutations producing an SCID phenotype and hypomorphic mutations presenting more variably.2, 7 Although autoimmunity is a known feature of aberrant RAG function, it has never been described as the primary manifestation of the disease in an infant. We describe a novel presentation of RAG deficiency characterized by the presence of B cells and early-onset autoimmunity.