HLA, Juvenile Rheumatoid Arthritis and Other Disease Associations

Abstract

The MHC lies within a small region of the 6th chromosome. Four loci are recognized (A, B, C and D). The genes at these loci control the expression of antigens found on the surface of nucleated cells. The presence of these cell surface antigens is determined by the use of specific antisera. Cell surface antigens expressed by the D locus are determined by the MLC reaction and by antisera to markers on B-lymphocytes, called B-cell alloantigens. The genes that control expression of cell surface antigens are either identical with or, more likely, located in close proximity to genes that control the production of serum complement components and various immunologic phenomena, such as graft-vs.-host reaction, delayed hypersensitivity, T-cell helper function, and T-cell suppressor function. The prevalence of certain cell surface antigens has been found to be increased in patients with certain diseases, including multiple sclerosis, insulin-dependent diabetes mellitus and psoriasis. In particular, there is a strong association between the presence of B27 cell surface antigen and ankylosing spondylitis, Reiter's disease and the spondylitis associated with psoriasis and inflammatory bowel disease. Much attention has been directed to the cell surface antigens of the A and B loci. The D locus antigens determined by MLC and by B-cell alloantigens may be more important as markers of disease susceptibility than those of the A and B loci. The D locus may be the immune response region. Associations with D locus markers have been made in rheumatoid arthritis, SLE, Sjögren's syndrome and JRA. In JRA, the greater prevalence of B27 cell surface antigen has been found to be associated with 2 particular subgroups. These include young males who develop peripheral arthritis and later spinal involvement compatible with ankylosing spondylitis and a second similar group with pauciarticular peripheral arthritis but without radiographic abnormalities of the sacroiliac joints or spine. The association of cell surface markers and disease susceptibility is one of the major discoveries of the century. Why do people get sick? Why do some people get sick while others do not? Causes of illness such as bacteria, viruses, carcinogens, and pollutants are omnipresent in our environment, but not all people exposed to environmental agents develop disease. Immune response may well determine whether we get sick or remain well. This response is surely controlled by genetic mechanisms. The process of understanding these mechanisms has only begun to unfold; this review has attempted to present the emerging picture.