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

He S, Zhu C, Liu Y, Xu Z, Sun R, Yang B, Guo X, Herrmann i M, Munoz LE, Gjertsson I, Holmdahl R, Dai L, Zhao Y (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 16

Article Number: 6692

Journal Issue: 1

DOI: 10.1038/s41467-025-62032-1

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.

Authors with CRIS profile

Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

West China Medical Center of Sichuan University / 四川大学华西医学中心 CN China (CN) Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset SE Sweden (SE) Karolinska Institute SE Sweden (SE)

How to cite

APA:

He, S., Zhu, C., Liu, Y., Xu, Z., Sun, R., Yang, B.,... Zhao, Y. (2025). A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis. Nature Communications, 16(1). https://doi.org/10.1038/s41467-025-62032-1

MLA:

He, Siyu, et al. "A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis." Nature Communications 16.1 (2025).

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