Immunogenetic aspects of juvenile chronic arthritis

The HLA associations of Juvenile Chronic Arthritis are reviewed in the light of the newest results. The most convincing data are available about the early onset pauciarticular Juvenile Chronic Arthritis (EOPA-JCA), where there are highly significant associations with 3 different regions of the HLA system: the HLA-A locus (HLA-A2), the HLA-DR/DQ region (HLA-DR5 and DR8 haplotypes) and the DP region (DPB1*0201). All these associations are independent of each other and not brought about by linkage disequilibrium. There are significant interactions between the associated alleles DPB1*0201 and DR5 haplotypes, DPB1*0201 and DR8 haplotypes as well as between A2 and DR5 and DR8 haplotypes, and between A2 and DPB1*0201. The association with the DR/DQ haplotypes reveal that most likely the DQA1 gene locus is primarily associated with JCA. There is a common motif which is present on all susceptible DQA1 alleles (0401, 0501, 0601) and not present on all the others (12). Taking all these information together, the following hypothesis is proposed: the observed HLA associations are a reflection of the direct involvement of the HLA genes in pathogenesis. The normal function of HLA molecules, namely the presentation of peptides of the T-cell receptor, is assumed to be a key mechanism in pathogenesis where an arthritogenic peptide is specifically bound by the DQ molecules, with binding specificity determined by the common motive on the DQA chain. It is possible that some of the arthritogenic peptides may be derived from self-histocompatibility antigens such as HLA-A2 and/or DPB1*0201.