Microsatellite analysis in rheumatoid arthritis synovial fibroblasts.
OBJECTIVE
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.
Kullmann
F
F
Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany.
Widmann
T
T
Kirner
A
A
Jüsten
H P
HP
Wessinghage
D
D
Dietmaier
W
W
Rüschoff
J
J
Gay
S
S
Schölmerich
J
J
Müller-Ladner
U
U
D048868:Adaptor Proteins, Signal Transducing; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein