Cysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritis

Abstract Background Numerous 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 se...

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Main Authors: Yong Fan, Xinlei Yang, Juan Zhao, Xiaoying Sun, Wenhui Xie, Yanrong Huang, Guangtao Li, Yanjie Hao, Zhuoli Zhang
Format: Article
Language:English
Published: BMC 2019-05-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13075-019-1906-y
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author Yong Fan
Xinlei Yang
Juan Zhao
Xiaoying Sun
Wenhui Xie
Yanrong Huang
Guangtao Li
Yanjie Hao
Zhuoli Zhang
author_facet Yong Fan
Xinlei Yang
Juan Zhao
Xiaoying Sun
Wenhui Xie
Yanrong Huang
Guangtao Li
Yanjie Hao
Zhuoli Zhang
author_sort Yong Fan
collection DOAJ
description Abstract Background Numerous 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. Methods A 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. Results A 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. Conclusions Serum 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 registration Combination Therapy Prevents the Relapse of RA, NCT02320630. Registered 19 December 2014,
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spelling doaj.art-986524cb23224c72a359f710abdfaadb2022-12-22T01:20:02ZengBMCArthritis Research & Therapy1478-63622019-05-012111910.1186/s13075-019-1906-yCysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritisYong Fan0Xinlei Yang1Juan Zhao2Xiaoying Sun3Wenhui Xie4Yanrong Huang5Guangtao Li6Yanjie Hao7Zhuoli Zhang8Department of Rheumatology and Clinical Immunology, Peking University First HospitalDepartment of Rheumatology and Clinical Immunology, Peking University First HospitalDepartment of Rheumatology and Clinical Immunology, Peking University First HospitalDepartment of Rheumatology and Clinical Immunology, Peking University First HospitalDepartment of Rheumatology and Clinical Immunology, Peking University First HospitalDepartment of Rheumatology and Clinical Immunology, Peking University First HospitalDepartment of Rheumatology and Clinical Immunology, Peking University First HospitalDepartment of Rheumatology and Clinical Immunology, Peking University First HospitalDepartment of Rheumatology and Clinical Immunology, Peking University First HospitalAbstract Background Numerous 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. Methods A 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. Results A 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. Conclusions Serum 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 registration Combination Therapy Prevents the Relapse of RA, NCT02320630. Registered 19 December 2014,http://link.springer.com/article/10.1186/s13075-019-1906-yRheumatoid arthritisCysteine-rich protein 61BiomarkerDisease activityTreatment response
spellingShingle Yong Fan
Xinlei Yang
Juan Zhao
Xiaoying Sun
Wenhui Xie
Yanrong Huang
Guangtao Li
Yanjie Hao
Zhuoli Zhang
Cysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritis
Arthritis Research & Therapy
Rheumatoid arthritis
Cysteine-rich protein 61
Biomarker
Disease activity
Treatment response
title Cysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritis
title_full Cysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritis
title_fullStr Cysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritis
title_full_unstemmed Cysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritis
title_short Cysteine-rich 61 (Cyr61): a biomarker reflecting disease activity in rheumatoid arthritis
title_sort cysteine rich 61 cyr61 a biomarker reflecting disease activity in rheumatoid arthritis
topic Rheumatoid arthritis
Cysteine-rich protein 61
Biomarker
Disease activity
Treatment response
url http://link.springer.com/article/10.1186/s13075-019-1906-y
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