Comprehensive studies of immunopathogenesis of X-linked lymphoproliferative syndrome (XLP) include: (1) virological testing with Monospot, heterophile, EB-specific markers (anti-early antigen, -viral capsid antigen), and EB nuclear-associated antigen (EBNA) antibodies, EB genome detection by filter cRNA/DNA and vDNA/DNA renaturation kinetic and in situ hybridization studies, spontaneous cell line establishment, and transformation of cord cells with throat washings; (2) genetic studies such as pedigree analysis, screening for XLP (challenging males at risk with OX 174), doing EBV-specific serology, measuring spontaneous and induced chromosomal breakage of leukocytes by sister chromatid exchange and karyotyping, performing linkage studies for Xga blood group, G-6PD, and HLA-DR; and (3) immunopathological studies including blood count and morphology, immunoglobulin quantitation, T- and B-cell subpopulation enumeration in an activated-cell sorter, in vitro evaluation for lytic/suppressor and memory cell activity by testing leukocyte migration inhibition to EBV antigens, T-cell inhibition of EBV-infected cell outgrowth and reverse hemolytic plaque formation, comparing responses to EBV and pokeweed mitogen, assaying interferon and thymosin, and studying all organs to identify the cells producing lesions. Clonality of malignant lymphoma (ML) is determined by using simultaneous cell surface marking, karyotyping, and EBNA staining of lymphoid cells to test the hypothesis that polyclonal infectious mononucleosis (IM) can convert to monoclonal ML via a specific cytogenetic error. The registries provide an opportunity for consultation, diagnosis, counseling, and therapy. Thirty-five kindreds have been identified with XLP including five newly discovered families this past year. New phenotypes including necrotizing lymphoid vasculitis, red cell aplasia and delayed onset of infectious mononucleosis have been discovered. Twenty-one males known to have XLP survive. We are monitoring the changes in immunologic responses pre- and post-EBV infection in males at risk to trace the progression of the immune deficiency. Various T-cell and NK defects including EBV-specific memory T cells are noted in these patients, which may account for the fatal lymphoproliferative diseases observed. Using limiting dilution analysis we have demonstrated a decreased frequency of T helper and suppressor cell populations in blood of XLP patients. Males with XLP produce human T-cell growth factor (TCGF) and that TCGF boosts EBV-specific cytotoxic T cells. We have studied chromosomal aberrations in malignant lymphomas, in patients with AIDS, and have found 8;14 reciprocal translocation. We have seen increased chromosomal breakage in pre-AIDS patients and in patients with XLP. These B cell neoplasms in AIDS contains EBV genome. (IP)
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