Background Rheumatoid arthritis (RA) is an autoimmune disease which leads to bone destruction. RA synovium secretes large amounts of matrix metalloproteinase (MMP) 3 which plays essential role in degradation of extracellular components and cartilage. Several studies reported that serum MMP-3 correlated with radiographic progression. However, little was known about the relationship of synovial MMP-3 and radiographic progression.
Objectives To explore the correlation of synovial MMP-3 and radiographic progression in RA.
Methods Patients with active RA were recruited and followed up at 1st, 3rd, 6thand 12th months. Serum MMP-3 was detected by ELISA and clinical data was collected simultaneously at baseline and each visit. X-ray assessment of hand/wrist was repeated and radiographic progression was defined as the increase of total Sharp score more than 0.5 from baseline to one year. Synovial tissues were obtained at baseline and serial tissue sections were stained with H&E and immunohistochemically for MMP-3, CD3, CD20, CD38, CD68and CD15. Krenn's synovitis score was assessed semi-quantitatively and the density of positive-staining cells were quantitatively determined.
Results (1) Twenty-six patients fulfilled 1 year follow-up, 81% were female, age (median and IQR, similarly hereinafter) was 49 (39–58) years, disease duration was 24 (12–66) months, disease activity SDAI was 36.3 (24.0–48.1), and 54% were treated with csDMARDs while 46% were treated with bDMARD.
(2) Eight (31%) patients had radiographic progression at 12th month. Histopathological analysis showed that subscore of lining hyperplasia, percentage of lining MMP3+ cells and sublining CD68+ macrophage count were significantly higher in progressive patients than non-progressive patients (all P<0.05). Univariate logistic regression showed that high level of synovial MMP-3 was a significant predictor of 1-year radiologic progression (P=0.044, OR=1.117, 95%CI: 1.003 to 1.244). ROC curve analysis showed that the tradeoff value of synovial MMP-3 for predicting 1-year radiographic progression was 49% with sensitivity 63% and specificity 83% (AUC=0.785, 95%CI: 0.595–0.975, P=0.023).
(3) Patients were divided into high (n=9) or low synovial MMP-3 groups (n=17) according to the tradeoff value. Serum MMP-3 at baseline was significantly higher in high synovial MMP-3 group than that in low synovial MMP-3 group [440 (246–609) ng/ml vs 152 (69–316) ng/ml, P=0.016], and the percentage of synovial MMP3+ cells positively correlated with serum MMP-3 at each visit (r=0.537–0.592, all P<0.05). Serum MMP-3 decreased to normal after 6 months in half patients of low synovial MMP-3 group while it continually elevated throughout 12 months in high synovial MMP-3 group (Fig. 1A).
(4)SDAI in both groups decreased during follow-up and showed no significant difference at each visit (all P>0.05, Fig. 1B). However, Fisher exact test showed obvious tendency that the percentage of progressive patients in high synovial MMP-3 group (55.6%) was higher than that in low synovial MMP-3 group (17.6%, P=0.078, Fig. 1C).
Conclusions Our results implied that synovial MMP-3 may be a predictor of radiographic progression in RA.
Acknowledgements This work was supported by National Natural Science Foundation of China (No.81471597), Specialized Research Fund for the Doctoral Program of Higher Education (No.20130171110075) and Guangdong Natural Science Foundation (No.S2013010014396).
Disclosure of Interest None declared