Autoantibody Signatures as Biomarkers of Interstitial Cystitis.

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PROJECT SUMMARY/ABSTRACT: Interstitial cystitis (IC) is a debilitating, chronic bladder syndrome. Currently, there are no validated biomarkers for IC. It is well established, however, that inflammation is associated with IC. Although autoimmunity is debated as a potential cause, certain aspects of IC suggest that it may play a role in initiating or sustaining the chronic inflammatory response evident in this disease. For example, autoantibodies have been detected in the sera of IC patients to a greater extent than in controls, and the variety of antigens recognized by autoantibodies in IC suggests that the degeneration of bladder epithelial cells that occurs may stimulate the production of autoantibodies. Thus, the presence of inflammation/autoimmunity in IC may allow the use of the body's own immune response as a means of identifying biomarkers of IC. Clearly, knowledge of these potential autoantigens might better enable a greater understanding of the pathobiology of IC, and facilitate the development or use of autoantibody signatures as potential diagnostic biomarkers. With all of the potential advantages, the Achilles heel of autoantibodies is their sensitivity. Lessons from autoimmune diseases show that typically only 15-20% of patients demonstrate a response to any given antigen. However, proteomics may hold the key to success because of its ability to provide the means to multiplex. By linking the responses to several antigens together, the sensitivity and specificity of the test increases considerably. Recently, we described the development and use of a reverse capture autoantibody microarray, a platform that immobilizes 500 specific antigens using a high-density monoclonal antibody capture array. These antigen targets are proteins that are involved in signal transduction, cell-cycle regulation, gene transcription, apoptosis, cell growth, receptors, membrane proteins, as well as adhesion and migration molecules. Using the immobilized antigens as baits, we can determine the autoantibody reactivity between test and controls to the immobilized antigens. We believe this platform may be well suited for the study of IC. Thus, the objectives of our research for this application are: 1) to test the hypothesis that the serum autoantibody repertoire from patients with IC can be exploited for autoantibody profiling, and 2) to determine the feasibility, robustness, and reproducibility of the reverse capture autoantibody microarray to identify autoantibody signatures as biomarkers of IC.