Abstract
Objective. To explore the correlation between matrix metalloproteinase- (MMP-) 3 and histological synovitis in rheumatoid arthritis (RA). Methods. Serum MMP-3 of 62 patients with active RA was detected by ELISA. Serial synovial tissue sections from all RA patients, 13 osteoarthritis, and 10 orthopedic arthropathies patients were stained with hematoxylin and eosin and immunohistochemically for MMP-3, CD3, CD20, CD38, CD68, and CD15. Results. The percentage of lining MMP3+ cells was significantly higher in RA patients especially with high grade synovitis and it was significantly correlated with Krenn's synovitis score (r = 0.574, P < 0.001) and sublining inflammatory cells. Multivariate stepwise linear regression analysis revealed that the association of the percentage of lining MMP3+ cells with activation of synovial stroma, sublining CD68+ macrophages, and CD15+ neutrophils was stronger than other histological indicators. The percentage of lining MMP3+ cells was significantly correlated with serum MMP-3 in RA (r = 0.656, P < 0.001). Serum MMP-3 was higher in RA patients with high grade synovitis than that of low grade synovitis and significantly correlated with synovitis score and activation of synovial stroma subscore (all P < 0.05). Conclusion. Serum MMP-3 may be an alternative noninvasive biomarker of histological synovitis and RA diagnosis.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis which leads to cartilage degradation, subchondral bone erosions, and eventual disability [1]
As histopathological features are the golden standard for diagnosis of synovitis, histological synovitis analysis is a powerful tool for clarifying the pathological change in synovium and immunochemical analysis of synovitis is helpful for the study of pathogenesis and prognostic evaluation [2, 3]
The percentage of lining MMP3+ cells was significantly higher in RA patients with high grade synovitis than that in RA patients with low grade synovitis, and synovial matrix metalloproteinase- (MMP-)3 expression was higher in high grade group of hyperplasia of lining layer, inflammatory infiltration, and activation of synovial stroma (Figure 2(a))
Summary
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis which leads to cartilage degradation, subchondral bone erosions, and eventual disability [1]. Several grading systems have been developed for scoring the histopathological features of synovitis in RA, which are useful in providing information combined with morphological and molecular data and giving basic and standardized diagnostic information concerning the inflammatory character of the diseases and the degree of inflammation [4,5,6,7]. Synovial tissue should be obtained by invasive techniques such as arthroscopy or blind needle biopsy, leading to limited histological measures in routine clinical practice. Alternative noninvasive measures such as serological biomarkers are required for synovitis assessment in daily clinical use
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