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 (1,465 +/- 939 (SD) ng/ml) was significantly higher (P < 0.001) than that in 7 control fluids (357 +/- 51 ng/ml). 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-amino-phenylmercuric acetate (APMA)-activated collagenase activities in 14 RA fluids were only a trace, 0.26 +/- 0.29 and 1.48 +/- 0.63 (SD) units/ml, respectively. After the column step, however, more than 20-fold (6.83 +/- 5.46 units/ml) and 10-fold (15.1 +/- 5.9 units/ml) higher collagenase activities were detected in non- and APMA-activated RA fluids, respectively.