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 measured 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 synthesis of MMP-9 in RA synovium. Clinical samples, subjected to gelatin substrate zymography, antigenic immunoassay, and a quantitative substrate 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. Immunostaining on fresh RA synovial specimens revealed MMP-9 within vascular walls in fibroblast-like cells and macrophages; mRNA synthesis was detected using reverse transcriptase in situ PCR. In summary, MMP-9 levels are substantially elevated in the sera and SF from patients with RA. The RA synovium is a source of this MMP-9 production, with abundant mRNA and protein observed within several different type of rheumatoid synovial cells.
Gruber
B L
BL
Department of Medicine, State University of New York, Stony Brook 11794-8161, USA.
Sorbi
D
D
French
D L
DL
Marchese
M J
MJ
Nuovo
G J
GJ
Kew
R R
RR
Arbeit
L A
LA
D000941:Antigens / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology; D015415:Biomarkers / Q000097:blood*; D017364:Collagenases / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9; D016133:Polymerase Chain Reaction; D013379:Substrate Specificity; D013582:Synovial Fluid / Q000201:enzymology
D000941:Antigens; D015415:Biomarkers; D017364:Collagenases; D020780:Matrix Metalloproteinase 9