Epstein-Barr virus (EBV) and X-linked lymphoproliferative syndrome (XLP)

XLP was first described in 1975, when EBV was still focused on as an immediate oncogenic agent, but with some uncertainties raised by the absence of EBV in most non-endemic Burkitt lymphoma. The discovery of XLP refreshingly evidenced and popularized the concept, "EBV pathogenicity (oncogenicity) in immunocompromised hosts", which was later vastly substantiated by EBV-carrying lymphomas in organ-transplanted and AIDS patients. Fatal (or severe) IM, acquired hypogammaglobulinemia (AH) and malignant lymphoma (MH) are 3 major phenotypes in XLP. Fatal IM occurs in 2/3 with a mortality rate of 85%. Lymphocyte infiltration (T cells and EBV-positive B cells) followed by their depletion with the appearance of macrophages. EBV-associated hemophagocytic syndrome in the bone marrow leads to hematocytopenia, ML, AH and ML with AH usually occur after EBV infection, but can occur before it. Reactivation pattern of EBV serology (high VCA, high EA, low EBNA), impaired generation of EBV-specific killer cell (poor regression), lowered NK activity, lowered 4/8 ratio and failure to mount IgG response to phi X174 have been recorded in XLP and carrier females. However, some or all of these are also found in non-XLP congenital immunodeficiencies as well as acquired immunodeficient states like advanced lymphoma or AIDS. In order to record XLP-specific defects, impaired help of autologous Ia-stimulated T4 cells or exaggerated suppression by T cells exposed to MA-pulsed macrophages is now being tested (Purtilo, personal communication). Fewer V region genes of T receptor may be a possibility. Restriction fragment length polymorphism (RFLP) by using probes from X chromosome may substantiate the precise genetics of this disease.