Recurrent B-cell non-Hodgkin's lymphoma in two brothers with X-linked lymphoproliferative disease without evidence for Epstein-Barr virus infection

We present two male siblings suffering from recurrent manifestations of B-c ell non-Hodgkin's lymphoma (NHL) and recurrent infections of the lower resp iratory tract associated with bronchiectasis. Immunodeficiency could not be demonstrated by any laboratory investigation. In both patients, lymphomas developed without evidence for Epstein-Barr virus (EBV) infection, i.e. no antibody response to EBV-specific antigens, negative EBV-PCR (polymerase ch ain reaction) in peripheral blood cells, and absence of latent membrane pro tein(LMP) and EBV-encoded RNA (EBER) in lymphoma cells. Molecular analysis of the SH2D1A, the gene for X-linked lymphoproliferative disease (XLP) led to the identification of a deletion in the first exon in both patients. The refore, we postulate that the genetic defect and the following dysregulatio n of the B-/T-cell interaction rendered these patients susceptible to the e arly onset of B-cell NHL and that EBV infection is not an obligate prerequi site.