C1q-containing immune complexes purified from sera of juvenile rheumatoid arthritis patients mediate IL-8 production by human synoviocytes: Role of C1q receptors

Immune complexes that vary in size and composition are present in the sera and synovial quid of juvenile rheumatoid arthritis (JRA) patients. They are believed to be potent inducers of the ongoing inflammatory process in JRA. However, the precise composition and role of these complexes in the pathop hysiology of JRA remain unclear, We hypothesized that circulating ICs have the potential to interact with resident joint synovial fibroblasts (synovio cytes) and induce the expression of inflammatory cytokines. To test this hy pothesis, cultures of synoviocytes from healthy individuals were treated wi th ICs isolated from the sera of JRA patients. Studies reported in this wor k demonstrate that IgM affinity-purified ICs from the sera of JRA patients contain IgM, Clq, IgG, and C3 to a variable extent, These ICs induce IL-8 m RNA and protein production in normal synoviocytes. Our data indicate that C lq in these ICs mediates, in part, IL-X induction in synoviocytes. This is based on our findings of Clq-binding proteins for collagen stalks (cC1qR) e nd globular heads (gC1q-binding protein) of Clq in synoviocytes. In additio n, collagen stalk and to some extent globular head fragments of Clq inhibit IC-mediated IL-8 induction in synoviocytes. Together, these findings provi de evidence for a novel mechanism of IL-8 production by synoviocytes, which could play a key role in inflammation by recruiting leukocytes to synovial tissue and fluid-and subsequently contributing to joint disease.