The histocompatibility complex and rheumatic diseases.

Histocompatibility typing has assumed an increasingly important role as a clinical and research tool in rheumatic diseases. The HLA antigens which are serologically defined (A and B series) are being used most extensively for clinical work, but the role of other immunologic determinants in the HLA complex is being evaluated. These include D-locus (MLC) determinants, several complement components, and immune response genes which have been well characterized in the mouse, but not in man. The products of the major histocompatibility complex are inherited in a simple Mendelian fashion as a series of co-dominant alleles. Large population studies have characterized the frequencies of various alleles, and family studies have allowed tentative mapping of the various loci within the complex on the sixth chromosome in man. A number of diseases which are considered to be autoimmune in nature are now known to be associated with specific HLA antigens. Of these disease associations, the strongest and best studied are the seronegative spondyloarthropathies which are highly associated with the B27 antigen. Included in this group are ankylosing spondylitis, Reiter's syndrome, psoriatic arthropathy, colitic arthropathy, Yersinia arthritis and a small group of juvenile rheumatoid arthritis patients with features of ankylosing spondylitis. The clinical application of tissue typing or B27 testing is most helpful in regard to difficult diagnostic problems in patients with early or atypical seronegative spondyloarthropathy. Its value as an indicator of prognosis, and its value in counselling family members is not well established. There are many interesting hypotheses regarding pathogenetic mechanisms of these rheumatic diseases based on susceptibility factors related to the major histocompatibility complex. An abnormal immune response gene within the complex is probably a key feature of the mechanism, but the exact details are little more than speculative at this point.