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.
IntroductionCore disease activity indicators of rheumatoid arthritis (RA) have been found to be limited in predicting joint destruction progression. Matrix metalloproteinase (MMP) 3 plays an essential role in joint destruction and was found elevated in some remission patients. We aimed to monitor dynamic core disease activity indicators and serum MMP-3 for one year and evaluate their value for predicting radiographic progression.MethodsPatients with active RA (Simplified disease activity index > 3.3) were treated according to the treat-to-target strategy. Serum MMP-3 was detected by enzyme-linked immunosorbent assay and clinical data were collected simultaneously at 0, 1st, 3rd, 6th and 12th month. X-ray assessment of hand/wrist was repeated at baseline and the 12th month and a change of total Sharp score > 0.5 units was defined as radiographic progression.ResultsFifty-six patients completed one year follow-up and 29 % showed radiographic progression. Although not significantly different at baseline, serum MMP-3 and all core disease activity indicators, except for erythrocyte sedimentation rate, at the 12th month were significantly higher in the progressive group than in the non-progressive group. Among sixteen progressive patients, 69 % achieved the therapeutic target and 56 % had continuous elevated serum MMP-3, 38 % had continuous elevated serum MMP-3 and normal C-reactive protein (CRP) at the 6th month. Log-rank tests and repeated measures analysis revealed a significant difference in dynamic serum MMP-3 between progressive and non-progressive patients. Receiver operating characteristic curve and univariate logistic regression analysis showed that elevated serum MMP-3 at 0, 1st, 3rd and 6th months, compared with CRP at the 1st month, were significant predictors for one-year radiographic progression (MMP-3 odds ratio (OR):10.500 ~ 27.000, all P < 0.05; CRP: OR = 7.400, P = 0.011).ConclusionsOur data showed that continuously elevated serum MMP-3 for 3 ~ 6 months predicted one-year radiographic progression which implied that monitoring of dynamic serum MMP-3 combined with core disease activity indicators may be more helpful for predicting radiographic progression and treatment decision in RA.
Synovial CD79a-positive B cells may be a helpful biomarker for histologic disease activity in RA and may be involved in the pathogenesis of joint destruction in RA.
Kimura's disease (KD) is a rare, benign, chronic inflammatory disease which typically presents as persisting or recurring tumor-like lesions in the head and neck area that can be easily misdiagnosed. We report one patient with KD treated with leflunomide in combination with glucocorticoids and analyzed the literature on treatment of KD. The patient had a recurrent mass in the left upper arm with eosinophilia and elevated serum IgE but no renal involvement. The clinical manifestations improved markedly within 1 month, and blood eosinophil count and serum IgE normalized. Corticosteroids were then tapered gradually without recurrence or severe side effects in the 2-year follow-up period. Literature analysis identified four different non-drug interventions and 18 different drugs for treating KD, most of which were obtained from case reports. Our use of combination therapy of leflunomide and glucocorticoids suggests the need for a controlled trial for the treatment of this rare disorder.
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