Significance of complement components C1q and C4 bound to circulating immune complexes in juvenile idiopathic arthritis: Support for classical complement pathway activation

摘要

Objective: Immune complexes (ICs) from sera of juvenile idiopathic arthritis (JIA) patients show increased complement opsonization; however, a definitive role for involvement of the classical or alternative pathway is not entirely clear. To delineate the role of these pathways, we measured activated complement products bound to circulating IC (CICs) in the sera of JIA patients. Methods: Sera from 100 JIA patients and 22 healthy children were collected. Clq, C4, C3, C3d, and membrane attack complex (MAC) bound to CICs were measured by enzyme-linked immunosorbent assay. Data was compared to IgM rheumatoid factor (RF), IgG anti-cyclic citrullinated peptide (CCP) antibodies, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels. Results: Mean levels of Clq, C4, and MAC bound to CICs were significantly elevated in JIA patients compared to healthy children. Clq correlated significantly with C4 and MAC bound to CICs and C4 and MAC also demonstrated significant correlation. No significant differences were noted in complement components bound to CICs when evaluating IgM RF, anti-CCP antibody, and CRP positivity. A significant correlation was noted between MAC bound to CICs and ESR. Clq and MAC bound to CICs mean levels were significantly higher in patients with an elevated ESR compared to those with a normal ESR level. Conclusion: JIA patients have elevated levels of complement components bound to CICs, particularly from the classical pathway. Moreover, classical pathway components were associated with ESR, a marker of disease activity. MAC bound to CICs also correlated significantly with ESR, further supporting the notion of complement-mediated tissue injury that is triggered by lC-mediated classical pathway activation.