Microsatellite analysis in rheumatoid arthritis synovial fibroblasts

Objectives-Rheumatoid arthritis (RA) is a chronic disease characterised by irreversible destruction of the affected joints. As aggressive transformed- appearing synovial fibroblasts are commonly found at the site of invasion o f the rheumatoid synovium into the adjacent cartilage and bone, the presenc e of microsatellite instability (MSI) and expression of mismatch repair enz ymes as a possible mechanism in the alteration of these cells was examined. Methods-DNA was extracted from the synovial fibroblasts and blood of 20 pat ients with long term RA undergoing joint replacement, and the presence of M SI was studied at 10 microsatellite loci. In addition, immunohistochemistry was performed to evaluate the expression of the two major mismatch repair enzymes (hMLH1 and hMSH2) in rheumatoid synovium. Results-MSI could not be detected in any of the fibroblast cell populations derived from the 20 different rheumatoid synovial samples. In addition, st rong expression of mismatch repair enzymes could be seen in numerous cells, including fibroblasts, throughout the synovium. Conclusions-Applying the currently used and established markers for MSI, th e data show for the first time that MSI does not appear to have an importan t role in alteration of rheumatoid synovial fibroblasts into an aggressive phenotype. On the other hand, strong mismatch repair enzyme synthesis in rh eumatoid synovium supports the hypothesis of continuing DNA repair, presuma bly due to long term, inflammation induced DNA damage.