Large-scale multicenter study reveals anticitrullinated SR-A peptide antibody as a biomarker and exacerbator for rheumatoid arthritis
Yang Xie, Chaonan Wei, Dongdong Fu, Wei Zhang, Yan Du, Chuncui Huang, S Liu, Ranran Yao, Zihao He, Shenghua Zhang, Jin Xu, Bin Shen, Lulu Cao, Ping Wang, Xiangyu Fang, Xi Zheng, Hongying Lin, Xihua Wei, Wenhao Lin, Mingxin Bai, Danxue Zhu, Yingni Li, Yamin Ding, Huaqun Zhu, Hua Ye, Jing He, Yin Su, Yuan Jia, Huaxiang Wu, Yongfu Wang, Dan Xing, Xiaoyan Qiu, Zhanguo Li, Fanlei Hu
Abstract
Current diagnosis and treatment of rheumatoid arthritis (RA) is still challenging. More than one-third of patients with RA could not be accurately diagnosed because of lacking biomarkers. Our recent study reported that scavenger receptor-A (SR-A) is a biomarker for RA, especially for anticyclic citrullinated peptide antibody (anti-CCP)-negative RA. Here, we further identified the B cell autoantigenic epitopes of SR-A. By a large-scale multicenter study including one training and three validation cohorts of 1954 participants, we showed that anticitrullinated SR-A peptide antibody (anti-CSP) was exclusively elevated in RA as a biomarker, particularly useful for seronegative RA. Combination of anti-CSP with anti-CCP demonstrated superior diagnostic value for RA, with sensitivity of 84.83% and specificity of 92.43%. Moreover, RA anti-CSP revealed distinct glycosylation patterns, capable of provoking inflammation in cartilage organoids and exacerbating disease progression in experimental arthritis. Together, these data identify anti-CSP as an RA autoantibody clinically applicable and actively involved in disease pathogenesis.