Natural autoimmunity in oligoarticular juvenile idiopathic arthritis

Abstract Oligoarticular juvenile idiopathic arthritis (oligo-JIA) is classically thought of as an antigen-driven lymphocyte-mediated autoimmune disease. Considering the major immunoregulatory role of natural antibodies (NAbs) in homeostasis and autoimmune pathogenesis, we designed this study to further elucidate their role in oligo-JIA pathogenesis. To this end, 70 children with oligo-JIA and 20 healthy matched controls were enrolled in the study. Serum IgM and IgA antibodies against human G-actin, human IgG F(ab΄) 2 fragments and the hapten TriNitroPhenol (TNP) were measured by in-house enzyme-immunoassays. In addition, total concentration for serum IgM and IgA was also measured by ELISA and in cases where significant differences were observed between groups, the ratio of NAbs levels to the total IgM and IgA concentrations was used for comparisons. The ratios of IgA anti-TNP, anti-actin and anti-F(ab΄) 2 levels to total serum IgA concentration were found to be significantly increased in patients with oligo-JIA compared to healthy subjects. Significantly elevated levels of IgM anti-TNP antibodies were also found in children with inactive oligo-JIA compared to those of children with active disease and healthy controls. In the presence of anterior uveitis, IgM anti-TNP levels were significantly higher than in patients without uveitis or in healthy controls. Backward regression analysis revealed than the disease activity and the presence of anterior uveitis independently affect IgM anti-TNP levels. Our findings are in accordance with the hypothesis that NAbs contribute to the pathogenesis of autoimmune diseases and provide additional evidence that disturbances in natural autoimmunity may contribute to the as yet unclarified pathogenesis of oligo-JIA.