DIAGNOSTIC AND THERAPEUTIC APPLICATION OF ANTI-IDIOTYPES TO AIDS RELATED AUTOANTIBODIES

SEVERAL RECENT STUDIES HAVE DEMONSTRATED A CORRELATION BETWEEN THE DEVELOPMENT OF AUTOANTIBODIES TO HELPER T CELLS AND DISEASE PROGRESSION IN HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTIONS. THE RESULTS OF THESE STUDIES HAVE ALSO INDICATED THAT THESE AUTOANTIBODIES MAY CONTRIBUTE TO THE PATHOGENESIS OF THE ACQUIRED IMMUNE DEFECIENCY SYNDROME (AIDS). THE MAIN OBJECTIVE OF THIS PROPOSAL IS TO DEVELOP CLINICALLY USEFUL ANTI-IDIOTYPE (ANTI-ID) MONOCLONAL ANTIBODIES (MOABS) TO THESE AIDS RELATED AUTOANTIBODIES. DURING THE PHASE I PERIOD, ANTI-IDS WILL BE GENERATED TO CYTOTOXIC AUTOANTIBODIES SPECIFIC FOR CD4+ LYMPHOCYTES ISOLATED FROM INDIVIDUALS INFECTED WITH HIV. THESE AUTOANTIBODIES AND ANTI-ID MOABS WILL BE UTILIZED TO DEVELOP IMMUNOASSAYS TO MEASURE SERUM AUTOANTIBODY LEVELS IN HIV INFECTED INDIVIDUALS AND CONTROL POPULATIONS. DETECTION OF ANTI-HELPER T CELL AUTOANTIBODIES WILL BE CORRELATED WITH AIDS RELATED DISEASE PARAMETERS AND THE CLINICAL COURSE OF HIV INFECTIONS. THESE STUDIES WILL BE CONTINUED INTO THE PHASE II PERIOD TO IDENTIFY THE ROLE OF THESE DIAGNOSTIC ASSAYS IN PREDICTING AIDS PROGRESSION IN HIV INFECTED INDIVIDUALS. IN ADDITION, AS ANTI-IDS HAVE BEEN UTILIZED TO INHIBIT AUTOIMMUNE RESPONSES, THE DEVELOPEDANTI-IDS MAY ALSO FIND FUTURE THERAPEUTIC APPLICATION IN THESUPPRESSION OF AUTOANTIBODIES WHICH MAY BE INVOLVED IN AIDS PATHOGENESIS. OVERALL, THE RESULTS OF THE PHASE I AND II STUDIES SHOULD LEAD TO THE DEVELOPMENT OF NOVEL DIAGNOSTIC ASSAYS AND THERAPEUTIC PRODUCTS WHICH MAY FIND FUTURE APPLICATION IN THE MANAGEMENT OF HIV INFECTIONS AND IN THE TREATMENT OF AIDS RELATED DISORDERS.