A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-07-21 DOI:10.1038/s41467-025-62032-1

Siyu He, Chenxi Zhu, Yi Liu, Zhiqiang Xu, Rui Sun, Bin Yang, Xin Guo, Martin Herrmann i, Luis E. Muñoz, Inger Gjertsson, Rikard Holmdahl, Lunzhi Dai, Yi Zhao

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Abstract

Rheumatoid arthritis (RA) is a systemic inflammatory condition posing challenges in identifying biomarkers for onset, severity and treatment responses. Here we investigate the plasma proteome in a longitudinal cohort of 278 RA patients, alongside 60 at-risk individuals and 99 healthy controls. We observe distinct proteome signatures in at-risk individuals and RA patients, with protein levels alterations correlating with disease activity, notably at DAS28-CRP thresholds of 3.1, 3.8 and 5.0. The combination of methotrexate (MTX) and leflunomide (LEF) modulates proinflammatory pathways, whereas MTX plus hydroxychloroquine (HCQ) impact energy metabolism. A machine-learning model is trained for predicting responses, and achieves average receiver operating characteristic (ROC) scores of 0.88 (MTX + LEF) and 0.82 (MTX + HCQ) in the testing sets. The efficiency of these models is further validated in independent cohorts using enzyme-linked immunosorbent assay data. Overall, our study unveils distinct plasma proteome signatures across various stages and subtypes of RA, providing valuable biomarkers for predicting disease onset and treatment responses.

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一项纵向队列研究揭示了类风湿关节炎临床发病和治疗反应前的血浆蛋白生物标志物

类风湿性关节炎（RA）是一种全身性炎症，在确定发病、严重程度和治疗反应的生物标志物方面提出了挑战。在这里，我们研究了278名RA患者的血浆蛋白质组，其中包括60名高危个体和99名健康对照者。我们在高危个体和RA患者中观察到不同的蛋白质组特征，蛋白质水平的改变与疾病活动相关，特别是DAS28-CRP阈值为3.1,3.8和5.0。甲氨蝶呤（MTX）和来氟米特（LEF）联合使用可调节促炎途径，而MTX加羟氯喹（HCQ）影响能量代谢。机器学习模型被训练用于预测反应，并在测试集中达到平均受试者工作特征（ROC）得分0.88 （MTX + LEF）和0.82 （MTX + HCQ）。使用酶联免疫吸附试验数据，在独立队列中进一步验证了这些模型的效率。总的来说，我们的研究揭示了不同阶段和亚型RA的不同血浆蛋白质组特征，为预测疾病发作和治疗反应提供了有价值的生物标志物。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.