Background Rheumatoid synovitis is a chronic progressive disease with an invasive and tissue destructive infiltrate of lymphocytes, macrophages and synoviocytes. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) produced by these cells play an important role in the remodelling of the articular tissue in rheumatoid arthritis (RA).
Objectives In the study we investigated whether the histological appearance of the disease could be predicted from the serum concentration of MMPs and their inhibitors.
Methods The study included tissue and serum samples taken from 37 patients with clinically active RA and 30 with osteoarthritis (OA). Two types of RA were distinguished after morphological analysis of synovial specimens. Twenty two samples presented only diffuse infiltrates of mononuclear cells without any further microanatomical organisation, whereas lymphocytic conglomerates with germinal centre-like structures were found in 15 specimens. Serum concentrations of stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1 and TIMP-2 were assessed by means of ELISA method.
Results The unique serum profiles of MMPs and TIMPs were determined in both histological types of RA synovitis. In comparison with OA patients constituting a control group, there were detected higher serum concentrations of MMP-3 and MMP-9 in RA patients (in both cases p < 0.001). Elevated concentrations of MMPs were found in the serum of RA patients with follicular synovitis than in those with diffuse (p < 0.01 and p < 0.001 respectively). Serum of RA patients presented also elevated levels of TIMP-1 and TIMP-2 in comparison with OA patients (p < 0.001 and p < 0.01 respectively). TIMP-1 dominated in the serum of RA patients with follicular synovitis comparing with those with diffuse (p < 0.05). The serum concentrations of MMPs and TIMP-1 could clearly identify patients with two different histological types of rheumatoid synovitis and with OA. The clinical data analysed in our study implicated that rheumatoid disease in patients with follicular synovitis was more severe than in those with diffuse infiltrates.
Conclusion The distinct histological appearance of rheumatoid synovitis correlated with serum profile of MMPs or TIMP-1 reflects varied clinical activity of the disease and confirms its heterogeneity. These associations also suggest that patients with different morphological forms of RA might require different treatment regimens.
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