PROPERTIES AND REACTIVITY OF IMMUNE COMPLEXES IN RHEUMATOID SYNOVIAL FLUID

A number of studies suggest that the formation of antigen-antibody complexes (i.e., immune complexes (IC)) in synovial fluid and synovial tissue are involved in maintaining the chronic inflammatory synovitis in joints of patients with rheumatoid arthritis (RA). The exact mechanism of this involvment is not well understood and has, for the most part, been limited to studies of the interaction of IC with the complement system. In the present study, we have examined the properties of IC in rheumatoid synovial fluid via density gradient centrifugation and Sepharose CL-6B chromatography and studied their interaction with circulating mononuclear cells. Three different fractions of IC were identified. The largest molecular weight form, fraction I (>1000KD) was predominately composed of IgG and IgM and contained both IgM-RF and IgG-RF. All three fractions of IC can bind Clq and stimulate human mononuclear cell prostaglandin E (PGE) production. Fraction I, IC bound Clq most readily while fraction III IC were the most effective stimulators of mononuclear cell PGE production. IC stimulation of mononuclear cell PGE production was inhibited by Staphylococcus protein A suggesting mediation via activation of Fc receptors. We also present preliminary evidence that IC fraction III exhibit a differential reactivity towards normal and RA mononuclear cells. Exposure of normal mononuclear cells to these complexes resulted in greater PGE production when compared to RA mononuclear cells. We further present preliminary evidence which suggests that IC Fraction III can induce normal and RA mononuclear cell IL-1 (MCF) activity. These data suggest that synovial fluid from RA patients contains IgG-IgG-RF IC which appears to be particularly reactive in stimulating normal mononuclear cell PGE production when compared to RA mononuclear cells. The results obtained from these observations could potentially enhance our understanding of the complex interaction between immune events and cartilage destruction associated with RA.