Xie Yang, Wei Chaonan, Fu Dongdong, Zhang Wei, Du Yan, Huang Chuncui, Liu Shuyan, Yao Ranran, He Zihao, Zhang Shenghua, Jin Xu, Shen Bin, Cao Lulu, Wang Ping, Fang Xiangyu, Zheng Xi, Lin Hongying, Wei Xihua, Lin Wenhao, Bai Mingxin, Zhu Danxue, Li Yingni, Ding Yamin, Zhu Huaqun, Ye Hua, He Jing, Su Yin, Jia Yuan, Wu Huaxiang, Wang Yongfu, Xing Dan, Qiu Xiaoyan, Li Zhanguo, Hu Fanlei
Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
Department of Rheumatology and Immunology, Xinxiang Central Hospital, Xinxiang, China.
Sci Adv. 2025 Jan 3;11(1):eadr8078. doi: 10.1126/sciadv.adr8078.
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.
类风湿关节炎（RA）的当前诊断和治疗仍然具有挑战性。超过三分之一的RA患者因缺乏生物标志物而无法得到准确诊断。我们最近的研究报告称，清道夫受体-A（SR-A）是RA的一种生物标志物，尤其是对于抗环瓜氨酸肽抗体（抗CCP）阴性的RA。在此，我们进一步鉴定了SR-A的B细胞自身抗原表位。通过一项大规模多中心研究，该研究包括一个由1954名参与者组成的训练队列和三个验证队列，我们发现抗瓜氨酸化SR-A肽抗体（抗CSP）作为一种生物标志物在RA中特异性升高，对血清阴性RA尤为有用。抗CSP与抗CCP联合使用对RA具有更高的诊断价值，敏感性为84.83%，特异性为92.43%。此外，RA抗CSP显示出独特的糖基化模式，能够在软骨类器官中引发炎症并加剧实验性关节炎的疾病进展。总之，这些数据表明抗CSP是一种临床上可应用的RA自身抗体，并且积极参与疾病发病机制。
