Elevated C3 anaphylatoxin levels in synovial fluids from patients with rheumatoid arthritis

Abstract

Because cleavage products of the third component of complement augment inflammation and may contribute to arthritis, we used a competitive inhibition radioimmunoassay to measure levels of the low molecular weight cleavage products of the third component of complement, C3a and C3adesArg, in 72 synovial fluid samples. Mean levels of C3a/C3adesArg were more than sevenfold higher in 41 patients who had rheumatoid arthritis than in 15 patients who had degenerative joint disease or 5 patients who had traumatic arthritis. Striking elevations were also present in 2 patients who had acute gouty arthritis. A calculation of the fraction of intraarticular C3 cleaved showed that the patients with rheumatoid arthritis had a mean C3 cleavage of 11.6 ± 11.0%, which was significantly higher than values of <1.5% for patients with degenerative joint disease or traumatic arthritis. In rheumatoid arthritis and gouty arthritis, specific immunoassay identified substantial quantities of the initial C3 cleavage fragments.

Human synovial mast cells. I. Ultrastructural in situ and in vitro immunologic characterization

“…This negative finding is of some interest because complement activation is a feature of RA (6), and elevated levels of anaphylatoxins (C5a and C3a) have been reported in synovial fluids from patients with synovitis (38,39). Although we cannot rule out the possibility of some specific damage to C5a receptors caused by the enzymatic procedure used to isolate HuSMC, the findings from our comparative studies with mast cells isolated from other tissues tend to exclude this.…”

“…In addition, the possibility that the underlying disease of the cell donor (13) or the drugs used before and during general anesthesia (26) might have affected the in vitro response of synovial mast cells cannot be excluded. C5a, a clinically relevant stimulus (38,39), did not cause histamine release from HuSMC. Thus, HuSMC and human lung mast cells are the only human mast cells identified so far that cannot be activated by anaphyla- Figure 10.…”

“…Heterogeneous effects of C5a on human synovial, heart, and skin mast cells. Complement activation and anaphylatoxin formation (C3a and CSa) occur in the synovial fluid of patients with various inflammatory arthritides (38,39). In 12 experiments, recombinant human C5a (rHuCSa) (lo-' to W6M) did not cause histamine release from HuSMC ( Figure 6).…”

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).…”