Ia antigens and susceptibility to rheumatoid arthritis

Since the first description of human leukocyte agglutination antibodies, knowledge of the major histocompatibility complex (MHC), particularly the Ia region, has grown immensely and it is now recognized as a major polymorphic multigene family involved in the regulation of immune response and disease susceptibility. This review examined the hypothesis that there is another level of complexity within the Ia system, beyond multiple loci and allelic series, that involves specific epitopes as the functionally important components of the Ia molecule. Certain of these epitopes are likely to be responsible for the regulation of immune responses and susceptibility to certain autoimmune diseases such as rheumatoid arthritis (RA). Evidence was presented that certain monoclonal antibodies recognize epitopes found in a significantly more positive association with susceptibility to RA than available markers such as DR4. Biochemical characterization of the Ia molecules bearing this epitope revealed that the same epitope was present on two different molecules. The possibility was considered that such epitopes are closely related but not identical to Ia determinants that are primarily involved in producing the abnormal immune state characterizing those with RA.