The HLA complex and its relationship to rheumatic diseases

The HLA complex has been shown to be involved in the regulation of several aspects of the immune response, and has been shown to be associated with several rheumatologic diseases. The mechanisms by which HLA molecules predispose to disease has been an area of intense interest. Recent work has provided some possible explanations for the lack of absolute associations between a particular disease and a particular HLA antigen. There is now some evidence to suggest that specific epitopes rather than entire class I or II molecules may be responsible for disease predisposition. Furthermore, it appears that these epitopes may be transferred between different class I and II molecules by a mechanism known as gene conversion. Work evaluating the influence of other genes, such as those for the T cell receptor, on disease susceptibility has just begun. Many of the rheumatic diseases are quite diverse in their presentation. If only one of a heterogeneous group of diseases is associated with an HLA antigen, study of the entire group of diseases will of necessity dilute the association. Better definitions of clinical subsets should lead to improved correlations of HLA and disease. Little is known of etiologic agents or pathogenesis. As our knowledge of the interaction of HLA antigens, T cell receptors, and etiologic agents increases, we will come closer to an understanding of the mechanisms by which these molecules predispose to disease.