DEVELOPMENT OF DIAGNOSTIC PROBES FOR AUTOIMMUNE DISEASE

A CHARACTERISTIC FEATURE OF MANY RHEUMATIC DISEASES IS THE PRESENCE OF CIRCULATING ANTINUCLEAR ANTIBODIES. ASSAYS BASED ON THE MEASUREMENT OF THESE ANTIBODIES ARE ESTABLISHED IN THE CLINICAL LABORATORY FOR THE DIAGNOSIS OF THESE DISEASES, BUT OFTEN WITHOUT THE BENEFIT OF HAVING WELL-CHARACTERIZED OR ISOLATED TARGET ANTIGENS. ONE SUCH AUTOIMMUNE DISEASE IS SCLERODERMA OR PROGRESSIVE SYSTEMIC SCLEROSIS. THE OBJECTIVE OF THIS PROPOSAL IS TO DEVELOP MORE SENSITIVE AND QUANTITATIVE ASSAYS FOR THE DISEASE BY DEFINING THE ANTIGEN AND ANTIBODY REAGENTS. IN PHASE I, TWO MAJOR SCLERODERMA-ASSOCIATED ANTIGENS, SCL-70 AND CENTROMERE, WILL BE ISOLATED AND DESCRIBED UTILIZING A NUMBER OF TECHNIQUES INCLUDING IMMUNOAFFINITY, CHROMATOGRAPHY, AND PROTEIN BLOTS. WITH THE PRODUCTION OF THESE ANTIGENS IN QUANTITY AND IN AN IMMUNOREACTIVE FORM, THE PURIFIED ANTIGENS WILL BE USED AS IMMUNOGENS IN THE PRODUCTION OF MONOCLONAL ANTIBODIES IN PHASE II TO INSURE A CONSTANT AND ABUNDANT SUPPLY OF ANTIBODIES FOR ANTIGEN ISOLATION AND ULTIMATELY ASSAY STANDARDIZATION. SIMILAR EFFORTS WILL BE DIRECTED TOWARD OTHER OF THE SCLERODERMA-ASSOCIATED ANTIGENS TO OBTAIN AN INCLUSIVE AND REPRESENTATIVE PANEL OF DIAGNOSTIC PROBES TO ENCOMPASS THE CLINICAL VARIANTS OF THIS DISEASE.