Complement activation in synovial fluid and tissue from patients with juvenile rheumatoid arthritis

Abstract

Synovial fluid (SF) and synovial tissue from 10 patients with juvenile rheumatoid arthritis were examined. The SFs were heterogeneous with respect to the degree of complement activation. Quantification of C3dg and the terminal complement complex revealed a positive correlation between activation of the early and the late parts of the cascade in all patients. The amount of C‐reactive protein and the number of white blood cells in the SF correlated significantly with the degree of complement activation. Weak deposits of C3, C3dg, or terminal complement complex were observed in a few vessels in the synovial tissue from 5 of the patients. There was no correlation between complement activity in SF and in the corresponding tissue. Furthermore, there was no correlation between clinical activity in the joints and the degree of complement activation. It is concluded that there is a discrepancy between synovial tissue and synovial fluid with respect to complement activation. C‐reactive protein may, to some extent, be responsible for activation in SF, and the accumulation of white blood cells may be due to complement activation products.

Evaluation of classical complement pathway activation in rheumatoid arthritis: Measurement of C1q–C4 complexes as novel activation products

“…Taking into account the molecular size of the C1q-C4 complexes and the ratio between synovial fluid concentration and plasma concentration, it is most likely that C1q-C4 complexes are produced locally in the joint, and that the plasma levels measured in RA are the result of spillover. This would explain the higher C1q-C4 plasma levels in patients with active disease, since complement activation in the joint is higher in these patients (5,6,38).…”

“…For example, levels of complement proteins are depressed in the synovial fluid of patients with RA, reflecting consumption of complement. Moreover, elevated levels of complement cleavage products, such as sC5b-9, C3a, Bb, and C1inh-C1s complexes, have been observed in synovial fluid (4)(5)(6)(7)(8)(9).…”

Complement membrane attack on nucleated cells: resistance, recovery and non-lethal effects

“…In rheumatoid arthritis elevated levels ofTCCs have been found in synovial fluid and in plasma Mollnes & Paus, 1986;Morgan et al, 1988b) and the MAC has been localized in rheumatoid synovium (Sanders et al, 1986a). In rheumatoid joints release of inflammatory mediators including arachidonic acid metabolites and cytokines into synovial fluid has been demonstrated and a role of these mediators in the causation or propagation of inflammation suggested (Hopkins et al, 1988).…”

Anti–cyclic citrullinated peptide antibodies from rheumatoid arthritis patients activate complement via both the classical and alternative pathways

“…Complement levels in the synovial fluid of RA patients can be lower than those in controls because of local consumption (17). Complement activation products such as sC5b-9, Bb, C3a, and C1 inhibitorC1s and C1q-C4 complexes have been shown to be increased in synovial fluid (18)(19)(20)(21)(22), and complement depositions in synovial tissue from RA patients can be visualized by immunohistochemistry (23). Recent genetic association studies have indicated that complement (C5 in one previous study [24]) may be involved in the pathogenesis of human RA.…”