Abstract
BackgroundNumerous preclinical studies have revealed a critical role of cysteine-rich 61 (Cyr61) in the pathogenesis of rheumatoid arthritis (RA). But there is little literature discussing the clinical value of circulation Cyr61 in RA patients. The aim of our study is to investigate the serum Cyr61 level and its association with disease activity in RA patients.MethodsA training cohort was derived from consecutive RA patients who visited our clinic from Jun 2014 to Nov 2018. Serum samples were obtained at the enrollment time. To further confirm discovery, an independent validation cohort was set up based on a registered clinical trial. Paired serum samples of active RA patients were respectively collected at baseline and 12 weeks after uniformed treatment. Serum Cyr61 concentration was detected by enzyme-linked immunosorbent assay. The comparison of Cyr61 between RA patients and controls, the correlation between Cyr61 levels with disease activity, and the change of Cyr61 after treatment were analyzed by appropriate statistical analyses.ResultsA total of 177 definite RA patients and 50 age- and gender-matched healthy controls were enrolled in the training cohort. Significantly elevated serum Cyr61 concentration was found in RA patients, demonstrating excellent diagnostic ability to discriminate RA from healthy controls (area under the curve (AUC) = 0.98, P < 0.001). In addition, the Cyr61 level in active RA patients was significantly lower than that in patients in remission/low disease activity, and it was inversely correlated with composite disease activity scores and almost all of the components in statistic. Further study in the validation cohort (n = 77) showed a significant increase of the Cyr61 level at 12 weeks in ACR responders (ACR20/50/70), while no significant change of the Cyr61 level from baseline was observed in non-responders.ConclusionsSerum Cyr61 levels were remarkably increased in RA patients compared with those in healthy controls. The Cyr61 concentration was inversely correlated with RA disease activity and upregulated in those therapeutic responders.Trial registrationCombination Therapy Prevents the Relapse of RA, NCT02320630. Registered 19 December 2014,
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes progressive articular damage, functional loss, and comorbidity [1]
It is noteworthy that emerging preclinical studies have discussed the important roles of cysteine-rich 61 (Cyr61) in rheumatoid arthritis (RA) pathogenesis, but there is little literature discussing the clinical value of circulation Cyr61 in RA patients
We demonstrated that serum Cyr61 was remarkably elevated in RA patients compared to healthy controls, which was consistent with previous preclinical studies showing overexpressed Cyr61 in RA synovial fluids as well as peripheral blood
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes progressive articular damage, functional loss, and comorbidity [1]. An increasing number of studies found elevated expression of Cyr protein in fibroblast-like synoviocytes (FLS), synovial fluid, and peripheral blood mononuclear cells from RA patients [5, 6]. A recent study demonstrated Cyr promoted vascular endothelial growth factor expression in osteoblasts through negative regulation of miR-126 via the PKC-α signaling pathway and increased endothelial progenitor cell angiogenesis in RA [10]. It is noteworthy that emerging preclinical studies have discussed the important roles of Cyr in RA pathogenesis, but there is little literature discussing the clinical value of circulation Cyr in RA patients. Numerous preclinical studies have revealed a critical role of cysteine-rich 61 (Cyr61) in the pathogenesis of rheumatoid arthritis (RA). The aim of our study is to investigate the serum Cyr level and its association with disease activity in RA patients
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