Tissue Inhibitor of Metalloproteinases and Collagenase Activity in Synovial Fluid of Human Rheumatoid Arthritis

The levels of tissue inhibitor of metalloproteinases (TIMP) in synovial fluid of rheumatoid arthritis (RA) were determined by use of a sandwich enzyme immunoassay recently developed. The average value in 84 RA fluids (1,465i936 (SD) ng/ml) was significantly higher (P<0.00l) than that in 7 control fluids (357i51 ng/rnl). Unexpectedly high active and total collagenase (EC 3. 4. 24. 7) activities were obtained after passage of RA fluid through an anti-TIMP monoclonal antibody-affinity column. Before the affinity column, non-and 4-aminophenylmercuric acetate (APMA)-activated collagenase activities in 14 RA fluids were only a trace, 0.26i 0.29 and l.48i0.63 (SD) units/ml, respectively. After the column step, however, more than 20-fold (6.83i5 .46 units/ml) and 10-fold (15 .1 i5 .9 units/ml) higher collagenase