THIS PROJECT WILL DEVELOP A TEST WITH PROSPECTIVE COMMERCIALAPPLICATION TO IDENTIFY PANCREATIC ISLET CELL ANTIBODIES (ICA) WHOSE PRESENCE IN HUMAN SERUM IS INDICATIVE OF PRE- INSULIN-DEPENDENT DIABETES MELLITIS (IDDM) OR ITS VERY EARLYSTAGES.

THIS PROJECT WILL DEVELOP A TEST WITH PROSPECTIVE COMMERCIALAPPLICATION TO IDENTIFY PANCREATIC ISLET CELL ANTIBODIES (ICA) WHOSE PRESENCE IN HUMAN SERUM IS INDICATIVE OF PRE- INSULIN-DEPENDENT DIABETES MELLITIS (IDDM) OR ITS VERY EARLYSTAGES. AS NO STANDARDIZED ANTIGEN SOURCE EXISTS, AND BECAUSE NO COMMERCIAL TEST IS CURRENTLY AVAILABLE FOR THIS SIGNIFICANT DISEASE STATE, IT IS PROPOSED TO DEVELOP A MONO-CLONAL ANTIBODY AGAINST ICA TO FACILITATE DETECTING THE LATTER IN PATIENT SERUM. PUBLISHED METHODS INVOLVING USE OFCADAVER PANCREAS TISSUE SECRETIONS OR THOSE OF OTHER MAMMALIAN SPECIES AS A TEST RESOURCE FOR ISLET CELL ANTI- BODIES ARE UNSATISFACTORY: THEY ARE TEDIOUS AND DIFFERENT FIXATION METHODS PRODUCE VARIABLE RESULTS. PHASE I RESEARCHWILL FOCUS ON: (1) SEPARATING IGG SUBCLASS 2 ICA, AND ITS FURTHER FRACTIONATION, BY USING ISLET CELLS AS AN IMMUNO- ADSORBENT, TO YIELD ISLET CELL-SPECIFIC ANTIBODY; (2) EVALUATION OF EACH MONOCLONAL ANTIBODY, DERIVED FROM THE ABOVE ANTIGENS VIA HYBRIDOMA TECHNOLOGIES, WITH THE MURINE TISSUE CULTURE ISLET CELL LINE RIN5F; AND (3) INITIAL DEVELOPMENT OF ELISA AND LATEX AGGLUTINATION TESTS. USING THE MONOCLONAL ANTIBODIES PROCURED, PHASE II WILL CONTINUE WITH PRODUCT DEVELOPMENT AND CLINICAL STUDIES TO EVALUATE OVERALL SENSITIVITY AND SPECIFICITY OF THE PRODUCTS.