X-linked lymphoproliferative syndrome.

Abstract

The X-linked lymphoproliferative (XLP) syndrome is characterized by a selective immunodeficiency to Epstein-Barr virus (EBV) manifested by severe or fatal infectious mononucleosis and acquired immunodeficiency. Prospective studies in males prior to EBV infection have demonstrate vigorous cytotoxic cellular responses, which are predominantly polyclonally activated alloreactive cytotoxic T cells. Cytotoxic T cells that recognize EBV-infected autologous B cells have been demonstrated. Fatal EBV infections in males with XLP usually result from extensive liver necrosis. Males who survive acute EBV infection demonstrate global cellular immune defects with deficient T-, B- and NK-cell responses. It is hypothesized that uncontrolled alloreactive T-cell responses triggered by EBV-transformed B cells result in the immunopathy of XLP. Genetic studies have demonstrated XLP to be genetically linked to restriction fragment length polymorphisms detected with the DXS42 and DXS37 probes (from Xq26-q27). These probes make detection of carrier females and presymptomatic (EBV-seronegative) XLP males possible. Treatment of males with XLP experiencing acute EBV infection has not been successful, and current efforts are directed at prophylaxis with intravenous gammaglobulin.