We propose to study: 1) The autoimmune antigenic determinants of the platelet membrane glycoprotein GP11b-GP111a-Ca++ complex, which appears to contain the platelet membrane autoantigens in many cases of the classic autoimmune thrombocytopenic purpura noted predominantly in women. 2) The mechanism of the recently discovered syndromes of immunologic thrombocytopenic purpura noted predominantly in male patients at risk for AIDS: homosexuals, narcotics addicts and multiply-transfused hemophiliacs; as well as these patients with AIDS. 1) We propose to characterize and isolate platelet membrane antigenic determinants by studying the binding of sera and platelet eluates to the GP11b-GP111a complex in its various associated and dissociated forms, and following enzymatic digestion. Intact antigenic determinants would be isolated by affinity chromatography. Recognition of autoimmune antigenic determinants may be helpful diagnostically as well as therapeutically. Autoimmune disease could be potentially cured if tolerance could be safely induced with specific platelet autoantigens. 2) Immunologic thrombocytopenic purpura in patients at risk for AIDS is different from classic ATP in that it is associated with a 95% incidence of anti-AIDS virus-related antibody, markedly elevated platelet-bound lgG and C3C4, circulating immune complexes and anti-F(ab'),2 antibodies (not tested in hemophiliacs). We propose to examine the mechanisms of thrombocytopenia by a) measuring reticulo-endothelial function, b) assaying platelet eluates for anti-platelet antibody, c) looking for platelet antigenic determinants. We plan to study the relationship between the development of the thrombocytopenia and exposure to the AIDS-related virus (ARV) by looking for a) cross-reactivity between anti-F(ab')2 antibody and anti-ARV antibody (?anti-idiotype antibody), b) cross-reactivity between anti-ARV antibody and platelets, c) presence of ARV or anti-ARV on platelets, d) relationship between the development of AIDS and the persistence of culturable ARV in thrombocytopenic patients who will develop or have developed AIDS, compared to those who have not. The experiments proposed would provide valuable information regarding the pathophysiology of 'retro-virus-induced' thrombocytopenia, and the prognosis of patients presenting with thrombocytopenia who are at risk for AIDS.
Showing the most recent 10 out of 60 publications
