Diagnostic Assays for Rheumatic Diseases

DESCRIPTION (provided by applicant): The diagnosis of systemic lupus erythematosus is a serious public health problem. Almost 90 percent of the 2,000,000 people who have been told that they have lupus do not fulfill the diagnostic criteria to classify a person as having lupus. The laboratory test used to screen for lupus is largely to blame. This antinuclear antibody test and its derivatives are very sensitive (>95 percent), but are not specific (<2 percent). Other serological tests for lupus are specific, but not sensitive (i.e., anti-native DNA and anti-Sm autoantibodies). Through fine specificity immunochemical work, peptides have been found that tend to be bound by normal sera and others that are bound by lupus sera. Our first goal is to develop these assays for commercial application. Less expensive antigen-antibody binding reagents and conditions suitable for commercial performance are sought. Four substrate chemistries will be explored. Other goals include developing peptide-based assays to replace existing assays for anti-Sm, anti-nRNP, and anti-Ro. Some preliminary data suggest that patients with lupus nephritis who do not respond to aggressive immunosuppressive therapy can be identified through a peptide-based solid phase assay. The development of this assay will also be explored. The successful completion of this project will lead to improved clinical care of patients with suspected systemic lupus erythematosus by helping make products available to the marketplace that will more precisely diagnose this disease and assist its management. PROPOSED COMMERCIAL APPLICATION: The products will be used to help diagnose systemic lupus erythematosus, to identify particular antibody systems with prognostic value, and to identify patients who are not likely to respond to immunosuppressive therapy.