Evidence map›Paper›PMID 40691443›Full record

ArticleNature communications2025

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

Siyu He, Chenxi Zhu, Yi Liu, Zhiqiang Xu, Rui Sun, Bin Yang, Xin Guo, Martin Herrmann I, Luis E Muñoz, Inger Gjertsson and 3 more

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Siyu He *Department of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0009-0007-4350-4232
Chenxi Zhu *Department of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0003-4740-585X
Yi Liu *Department of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0009-0000-6283-8229
Zhiqiang Xu *Department of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0002-8133-1228
Rui Sun *Department of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0009-0003-2059-7721
Bin YangDepartment of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xin GuoDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Martin Herrmann IDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0002-0258-2484
Luis E MuñozDepartment for Internal Medicine 3, University Hospital Erlangen, and Deutsches Zentrum für Immuntherapie; Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.ORCID http://orcid.org/0000-0002-5395-804X
Inger GjertssonDepartment of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Rikard HolmdahlSection of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-4969-2576
Lunzhi DaiDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. lunzhi.dai@scu.edu.cn.ORCID http://orcid.org/0000-0002-3003-8910
Yi ZhaoDepartment of Rheumatology and Immunology and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. zhaoyi-rheuma@wchscu.cn.ORCID http://orcid.org/0000-0002-8522-8906

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82073221 and 31870826
6 · The paper itself

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.

Indexed as

Arthritis, RheumatoidBiomarkersBlood ProteinsAdultAgedAntirheumatic AgentsCase-Control StudiesFemaleHumansHydroxychloroquineLeflunomideLongitudinal StudiesMachine LearningMaleMethotrexateMiddle AgedAntirheumatic AgentsBiomarkersBlood ProteinsHydroxychloroquineLeflunomideMethotrexateProteome

Identifiers

PMID40691443
PMCPMC12279936

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.