Pathogenesis of juvenile chronic arthritis: genetic and environmental factors

Juvenile chronic arthritis (JCA) is a heterogeneous group of chronic arthropathies aVecting approximately 1-3 children per 1000. The initial oversimplified classification into pauciarticular, polyarticular, and systemic onset types has been expanded in a World Health Organisation-International League Against Rheumatism report to include seven diVerent types of disease. 1 It is clear that the majority of children with JCA have a diVerent disease from adults with rheumatoid arthritis, although the chronic arthropathies have some common clinical and pathological features. As a group, these diseases are generally considered to be autoimmune in origin with the evidence supporting this varying between types. There is a general female preponderance, characteristic chronic inflammatory infiltrates in the synovium and immune responses characterised by autoantibodies including antinuclear antibodies (ANA), IgM rheumatoid factor, and antibodies to heat shock proteins and the oncoprotein DEK. In addition and in common with many other autoimmune diseases, there are extensive and well documented associations with genetic markers, primarily, but not exclusively, within the major histocompatibility complex (MHC) or HLA region on the short arm of chromosome 6. It is anticipated that environmental triggering agents are also involved in the pathogenic process. In a recent review of a related disease, rheumatoid arthritis, the contribution of HLA genetics to pathogenesis was estimated to be approximately 37% with as yet unknown genes contributing further, with the balance being deemed largely due to environmental factors.