3 Juvenile arthritis: genetic update

Juvenile arthritis (JA) is a term that covers a number of different disease entities, of which only three present with significant Human Leukocyte Antigen (HLA) associations. (1) Pauciarticular JA with late onset and a strong male proponderance is associated with HLA-B27 and represents the group of juvenile spondyloarthropathies related to adult ankylosing spondylitis. (2) Early onset pauciarticular JA with a preponderance of females and a frequent occurance of chronic iridocyclitis and the frequent presence of anti-nuclear antibodies is associated with alleles from three different regions of the HLA system: HLA-A2 , which shows a very strong correlation with early age of onset; DR8, DR11 and DR12 as well as DQA1*0401, *0501, *0601 and finally DPB1*0201 . These alleles show no linkage disequilibrium in the control population. (3) Rheumatoid factor positive polyarticular JA is associated, as is adult rheumatoid arthritis, with DR4 . Concerning the possible mechanisms of the immunopathogenesis, it is speculated that the normal function of HLA molecules, namely the presentation of antigenic peptides, plays a major role. Data collected on HLA associations in early onset pauciarticular JA have been interpreted as indicating that alleles of the DQA1 locus ( *0401, *0501, *0601 ) are probably responsible for presenting the hypothetical arthritogenic peptides. It is speculated that the pathogenic process includes the presentation of HLA-A2 or HLA-DPB1*0201 derived peptides presented by DQ molecules. It is clearly stated that typing for HLA alleles has very little or no importance for clinical diagnosis and prognosis.