Immunological aspects of juvenile rheumatoid arthritis

This article reviews the evidence from recent studies on immunological abnormalities associated with pathophysiologic mechanisms operating in three clinical subtypes of juvenile rheumatoid arthritis (JRA) (polyarticular, pauciarticular and systemic). The main discussion is focused on three hallmarks of immunopathological studies. First, abnormalities in phenotype and function of lymphocytes from peripheral blood and inflamed synovium are discussed. The aberrations of lymphocytes are elucidated by T and B cells expressing phenotypic cell-markers such as CD20, CD21, CD4, CD8 and DR in association with different subtypes and disease activity. The functional imbalance and impairment of T and B cells are mainly observed by abnormal proliferation and/or in vitro Ig production in response to mitogens and alloantigens. Second, because the appearance of rheumatoid factors (RF) in serum indicates that the pathogenesis of JRA may be based on the autoimmune mechanism, the prevalence of RF including IgM, IgA and IgG isotype, hidden IgM RF and cross-reactive idiotype RF, and their characteristic properties are discussed. Moreover, specific auto-antibodies (antinuclear antibodies and others) for JRA are illustrated in this paper. Third, the production of various pro-inflammatory cytokines resulting in the release of tissue-damaging chemical mediators is also discussed. This may play a central role in the generation of systemic inflammation and joint involvement in JRA.