Immunogenetics of early onset pauciarticular juvenile rheumatoid arthritis

Abstract

Certain major histocompatibility complex (MHC) class I and class II genes are uniquely associated with early onset pauciarticular juvenile rheumatoid arthritis (JRA). As in other autoimmune diseases, these associations are likely to reflect contributions of the MHC to a trimolecular complex formed by HLA, lymphocyte T cell receptor and the putative antigen. The HLA genes associated with JRA are currently the best understood component of this complex. Recent findings demonstrated that combinations of genes, even within class II, play an important role. Data generated by DNA sequencing techniques have clarified the splits of given genes involved in disease, e.g., the HLA-DRw8 allele, HLA-DRB1*0801 rather than HLA-DRB1*0802, which does not carry an increased risk for disease. Recent findings suggest that aberrant sequences in particular genes are unimportant. Substantial challenges remain; including establishing the particular HLA DNA nucleotides critical to antigen presentation. It is probable that new and specific therapeutic approaches will be developed which will utilize the immunogenetic data now being accumulated.