A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis
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 contro...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62032-1 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Siyu He |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-228ea60437324eae8686d5ed6a3f80c6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-228ea60437324eae8686d5ed6a3f80c62025-08-20T03:43:10ZengNature PortfolioNature Communications2041-17232025-07-0116111610.1038/s41467-025-62032-1A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritisSiyu He0Chenxi Zhu1Yi Liu2Zhiqiang Xu3Rui Sun4Bin Yang5Xin Guo6Martin Herrmann i7Luis E. Muñoz8Inger Gjertsson9Rikard Holmdahl10Lunzhi Dai11Yi Zhao12Department of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Laboratory Medicine, West China Hospital, Sichuan UniversityDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment for Internal Medicine 3, University Hospital Erlangen, and Deutsches Zentrum für Immuntherapie; Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)Department of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of GothenburgSection of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska InstituteDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityAbstract 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.https://doi.org/10.1038/s41467-025-62032-1 |
| spellingShingle | 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 A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis Nature Communications |
| title | A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis |
| title_full | A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis |
| title_fullStr | A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis |
| title_full_unstemmed | A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis |
| title_short | A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis |
| title_sort | longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis |
| url | https://doi.org/10.1038/s41467-025-62032-1 |
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