Pathogenesis of juvenile chronic arthritis: genetic and environmental factors

Juvenile chronic arthritis (JCA) is a heterogeneous group of chronic arthropathies affecting 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 different types of disease.1 It is clear that the majority of children with JCA have a different 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.2 The purpose of this review is to consider the relative contributions of genetic versus environmental factors as being causal in the various types of JCA. JCA is rarely familial so that a low index of suspicion for a simple genetic basis is in order. In early studies reported, Dr Barbara Ansell and Professor Eric Bywaters were able to identify family disease and concordance in twins. Subsequently multiplex families and sibling …