Extended reports
Complement C1s activation in degenerating articular cartilage of
rheumatoid arthritis patients: immunohistochemical studies with an
active form specific antibody
a The Division of
Biology and Oncology, National Institute of Radiological Sciences,
Chiba, Japan, b The Department of Orthopaedic Surgery, Chiba
University School of Medicine, Chiba, Japan
Correspondence to: Dr H Sakiyama, Division of Biology and Oncology, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263 Japan.
Accepted for publication 30 September 1998
OBJECTIVE
The first
complement component C1s was reported to have novel functions to
degrade matrix components, besides its activities in the classic
complement pathway. This study explores participation of C1s in
articular cartilage degradation in rheumatoid arthritis (RA).
METHODS
Normal
articular cartilage (n=6) and cartilage obtained from joints with RA
(n=15) and osteoarthritis (OA, n=10) were immunostained using anti-C1s
monoclonal antibodies PG11, which recognises both active and inactive
C1s, and M241, which is specifically reactive to activated C1s. The
effects of inflammatory cytokines on C1s production by human articular
chondrocytes were also examined by sandwich ELISA.
RESULTS
In normal
articular cartilage, C1s was negative in staining with both PG11 and
M241. In contrast, degenerating cartilage of RA was stained with PG11
(14 of 15 cases), and in most of the cases (13 of 15 cases) C1s was
activated as revealed by M241 staining. In OA, C1s staining was
restricted in severely degrading part of cartilage (5 of 10 cases), and
even in that part C1s was not activated. In addition, C1s production by
chondrocytes in vitro was increased by an inflammatory cytokine, tumour
necrosis factor
.
CONCLUSION
These
results suggest that C1s activated in degenerative cartilage matrix of
RA but not in that of OA. C1s is thought to participate in the
pathogenesis of RA through its collagenolytic activity in addition to
the role in the classic cascade.
© 1999 by Annals of the Rheumatic Diseases
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