MARKEDLY ELEVATED SERUM MMP-9 (GELATINASE-B) LEVELS IN RHEUMATOID-ARTHRITIS - A POTENTIALLY USEFUL LABORATORY MARKER

In an attempt to find a potentially useful serum marker in rheumatoid arthritis (RA) which reflects underlying pathogenic mechanisms, we mea sured the circulating levels of matrix-degrading metalloproteinase-9 ( MMP-9), also termed gelatinase B, in sera and synovial fluid (SF) from patients with RA and also quantitated the deposition and local synthe sis of MMP-9 in RA synovium. Clinical samples, subjected to gelatin su bstrate zymography, antigenic immunoassay, and a quantitative substrat e degradation assay, revealed elevated 92- and 72-kDa proenzyme forms of MMP-9 and MMP-2 in RA sera and SF compared with healthy controls. I mmunostaining on fresh RA synovial specimens revealed MMP-9 within vas cular walls in fibroblast-like cells and macrophages; mRNA synthesis w as detected using reverse transcriptase in situ PCR. In summary, MMP-9 levels are substantially elevated in the sera and SF from patients wi th RA. The RA synovium is a source of this MMP-9 production, with abun dant mRNA and protein observed within several different type of rheuma toid synovial cells. (C) 1996 Academic Press, Inc.