Microsatellite analysis in rheumatoid arthritis synovial fibroblasts

Kullmann, Frank and Widmann, Thomas and Kirner, Alexander and Juesten, Hans-Peter and Wessinghage, Dieter and Dietmaier, Wolfgang and Rueschoff, Josef and Gay, Steffen and Schoelmerich, Juergen and Mueller-Ladner, Ulf (2000) Microsatellite analysis in rheumatoid arthritis synovial fibroblasts. ANNALS OF THE RHEUMATIC DISEASES, 59 (5). pp. 386-389. ISSN 0003-4967

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Abstract

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 of the rheumatoid synovium into the adjacent cartilage and bone, the presence of microsatellite instability (MSI) and expression of mismatch repair enzymes as a possible mechanism in the alteration of these cells was examined. Methods-DNA was extracted from the synovial fibroblasts and blood of 20 patients with long term RA undergoing joint replacement, and the presence of MSI 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, strong 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, the data show for the first time that MSI does not appear to have an important role in alteration of rheumatoid synovial fibroblasts into an aggressive phenotype. On the other hand, strong mismatch repair enzyme synthesis in rheumatoid synovium supports the hypothesis of continuing DNA repair, presumably due to long term, inflammation induced DNA damage.

Item Type: Article
Uncontrolled Keywords: HEREDITARY NONPOLYPOSIS; COLORECTAL CARCINOMAS; MISMATCH REPAIR; INSTABILITY; ADENOCARCINOMA; CANCERS; DNA;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Orthopädie
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 03 May 2022 13:57
Last Modified: 03 May 2022 13:57
URI: https://pred.uni-regensburg.de/id/eprint/42497

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