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a Department of
Internal Medicine I, University of Regensburg, D-93042 Regensburg,
Germany, b Department of Orthopaedics, University of
Regensburg, c Department of Pathology, University of
Regensburg, d Department
of Rheumatology, University Hospital, CH-8091 Zürich, Switzerland
Correspondence to: Dr Müller-Ladner Email: ulf.mueller-ladner{at}klinik.uni-regensburg.de
Accepted for publication 29 November 1999
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.
METHODSDNA
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.
RESULTSMSI
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.
CONCLUSIONSApplying
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.
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