Human autoantibodies as reagents in biomedical research

Abstract  Autoantibodies are typically associated with autoimmune diseases. In some instances the association of specific autoantibodies to a specific autoimmune disease have made their detection invaluable in clinical diagnosis. However, certain autoantibodies show no specific disease association and therefore have limited clinical utility. Nevertheless, autoantibodies are powerful tools for identification, characterization, and functional studies of their cognate antoantigens. In addition, the study of autoantibodies and their cognate autoantigens in human disease and in experimental animal models can provide valuable insight into disease mechanisms and the factors that ameliorate or reverse disease. This review will focus on three specific sets of autoantibodies, which were initially selected for investigation purely on the basis of their novel patterns of reactivity. These were observed when they were applied to a diagnostic HEp-2 test slide for antinuclear antibody detection by indirect immunofluorescence. The target autoantigens were identified as the trans-Golgi network protein GOLGA4 (Golgin 245 or p230), the early endosome antigen-1 (EEA1) and a yet to be identified and fully characterized phosphoepitope(s) restricted to chromosomal arms of condensed mitotic/meiotic chromosomes (MCA1). This laboratory has exploited sera which are reactive to these autoantigens for their identification and characterization, and in functional studies. This review highlights the uses of autoantibodies that may have limited diagnostic or prognostic utility, but are nonetheless novel reagents in the prosecution of molecular cell biology.