Parallel Assays for Anti-Ro Peptide Diagnostics

DESCRIPTION (provided by the applicant): Diagnosis of rheumatic diseases is inefficient, time consuming, and frustrating. Indeed, many patients suffer unnecessarily. We wish to develop a parallel assay system for the serology of autoimmune rheumatic diseases involving multiple analytes (on the order of 1,500 per assay performed) by concentrating upon the anti-Ro autoantibody system. Anti-Ro is associated with systemic lupus erythematosus, Sjogren's syndrome, subacute acute cutaneous lupus, congenital complete heart block, and neonatal lupus dermatitis. In addition, up to 1% of the adult female population has developed these autoantibodies. Anti-Ro autoantibodies are clearly very important. The details of the fine specificity of anti-Ro have great potential to provide information that can help provide diagnostic insight, prognostic evaluation, and assess disease risk. This project has three goals. First, we will adapt anti-Ro detection to a new technology. Second, we will attempt to reproduce our previous data with the new technology. Third, we will exploit the efficiencies of the new technology to much more completely define anti-Ro fine specificity and to use the aggregate data to design useful new products. We will adapt existing technology to detect antibodies against the particular epitopes of Ro, using fiber optic microspheres in parallel array. Compared to currently employed methods, this technology will allow as much as a 1,000-fold increase in throughput, a 1,500-fold decrease in reagents and serum required for assay, and a 500-fold decrease in per analyte cost. Preliminary data have identified a putative initial epitope in the anti-Ro autoimmune response and show a close immunologic relationship to a possible etiologic agent. We will explore the advantages of this technology to reveal the relationships between peptide-defined epitopes of Ro and putative precursor antigens, the progression of the autoimmune response, and the disorders associated with anti-Ro with the hope of developing commercially useful new diagnostics, in addition to the obvious research opportunities that understanding these relationships would offer.