The role of gelatinase-B and its tissue inhibitor of metalloproteinase-1 in rheumatic diseases

Abstract EN

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with systemic features and joint involvement, resulting in erosive synovitis, cartilage degradation and joint destruction.

The underlying molecular basis for matrix degradation is thought to be dependent on the action of a variety of proteolytic enzymes which may be elicited by both soft and hard tissue elements as well as by inflammatory cells.

One of the suggested contributory factors to the development of dermal fibrosis in scleroderma is a decrease in collagenase activity, which may be related to levels of serum tissue inhibitors of metalloproteinase-1 (TIMP-1).

Objective: To find out the role of gelatinase-B (metalloproteinase-9 (MMP-9)) and the level of the tissue inhibitor metalloproteinase-1 (TIMP-1) in the serum and synovial fluid of RA patients and serum of systemic lupus erythematosus and scleroderma patients (SSc), in an attempt to provide more insight into the role of matrix metalloproteinase in the pathogenesis of different rheumatic diseases and correlate both serum and synovial levels of both with the indices of disease activity and severity in RA patients.

Results: The serum levels of MMP-9 were found to be significantly higher in RA patients as compared with SLE patients, SSc patients and healthy controls.

The serum levels of MMP-9 were found to correlate positively with their synovial fluid MMP-9 levels (p<0.01), activity grade (p<0.01), ESR (p<0.05), Ritchie score (p<0.01).

Also, there were significant correlation between SF MMP-9 levels and activity grade (p < 0.01), Ritchie score (p < 0.05) and severity score (p<0.05), in RA patients.

Moreover, the serum levels of TIMP-1 in RA were found to be significantly elevated as compared with SLE, SSc and healthy controls, but did not correlate with the activity grade of the disease or any marker of disease activity in RA.

The serum level of TIMP-1 was higher in SSc patients with diffuse cutaneous involvement in comparison to normal controls, while, it was normal in SLE patients.

There was a significant increase in serum MMP-9 and TIMP-1 in SSc patients in comparison to normal controls, while there was no significant increase in both MMP-9 and TIMP-1 in SLE patients.

Conclusion: MMP-9 and TIMP-1 appear to play an important role in the pathogenesis of cartilage destruction and joint inflammation in RA.

Moreover, serum MMP-9 might serve as an additional marker for RA disease activity and severity.

In addition, tissue matrix accumulation in SSc is due to increased inhibitor rather than to decreased MMP and that TIMP-1 is involved in the pathogenesis of SSc.