HLA system and rheumatic disease.

Over 50 HLA antigens are now recognisable. Since we each have four antigens there are millions of possible combinations that characterise us as individuals. In humans these antigens are coded for in the major histocompatibility complex on the sixth chromosome. The loci for three of the complement components (C2, C4, and factor B) are in or near the major histocompatibility complex. In mice and other animals many genes controlling specific immune responses segregate in the same region as the genes for histocompatibility antigens. Equivalent human immune response genes have not yet been positively identified. Studies of inbred mouse strains have revealed a histocompatibility antigen (H-Y) controlled by the male Y chromosome, and there is good evidence that the H-Y antigen is present in man. In mice certain histocompatibility antigens are associated with susceptibility to particular diseases, the best examples being acute lymphocytic choriomeningitis, autoimmune thyroiditis, and leukaemia produced by viruses. The list of human diseases associated with HLA antigens grows day by day and includes disorders as diverse as multiple sclerosis, coeliac disease, psoriasis, juvenile diabetes, and haemochromatosis (Dausset and Svejgaard, 1977). The mechanisms by which HLA antigens may be associated with disease susceptibility have been the subject of extensive investigation and speculation. Some believe that the antigens play a direct part in disease processes, acting by mechanisms yet to be agreed. Alternatively, the importance of the HLA antigens may be in the close association of their heredity with other, more relevant, gene products. Since the genetic region between HLA-B and HLA-D is expected to contain immune response genes this may explain why most disease associations established so far have been with B or D antigens.