Identification of anti-herpes simplex virus antibody-producing B cells in a patient with an atypical RAG1 immunodeficiency

Mutations of the RAG1 or RAG2 protein that eliminate their recombination ac tivity result in T-B-severe combined immunodeficiency (SCID), whereas mutat ions retaining partial recombination activity lead to Omenn syndrome, a pec uliar SCID characterized by increased host T cells and absence of circulati ng B cells. The prognosis of this disease is fatal, unless hematopoietic st em cell transplantation is performed. This study reports a case of atypical SCID, carrying RAG1 mutations. The patient survived for 6 years without he matopoietic stem cell transplantation. The missense mutation, tested by in vivo recombination assay, revealed residual recombination activity. By the age of 5 years, the patient developed host B cells, but not T cells, possib ly due to engrafted maternal T cells. In addition, the host B cells were ab le to produce antibodies, including anti-herpes simplex virus-antibodies. T he fact that host B cells could produce antibodies in this patient could ex plain not only the mild phenotype observed but also, at least In part, how patients with Omenn syndrome produce Immunoglobulin E and sometimes Immunog lobulin M, as the same missense mutation of RAG1 gene has been reported In a patient with Omenn syndrome. (C) 2001 by The American Society of Hematolo gy.