Ling, S.F. orcid.org/0000-0001-8148-2344, Yap, C.F., Nair, N. orcid.org/0000-0001-9829-792X et al. (7 more authors) (2023) A proteomics study of rheumatoid arthritis patients on etanercept identifies putative biomarkers associated with clinical outcome measures. Rheumatology. kead321. ISSN 1462-0324
Abstract
Objectives Biologic DMARDs (bDMARDs) are widely used in patients with RA, but response to bDMARDs is heterogeneous. The objective of this work was to identify pretreatment proteomic biomarkers associated with RA clinical outcome measures in patients starting bDMARDs.
Methods Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to generate spectral maps of sera from patients with RA before and after 3 months of treatment with the bDMARD etanercept. Protein levels were regressed against RA clinical outcome measures, i.e. 28-joint DAS (DAS28) and its subcomponents and DAS28 <2.6 (i.e. remission). The proteins with the strongest evidence for association were analysed in an independent, replication dataset. Finally, subnetwork analysis was carried out using the Disease Module Detection algorithm and biological plausibility of identified proteins was assessed by enrichment analysis.
Results A total of 180 patients with RA were included in the discovery dataset and 58 in the validation dataset from a UK-based prospective multicentre study. Ten individual proteins were found to be significantly associated with RA clinical outcome measures. The association of T-complex protein 1 subunit η with DAS28 remission was replicated in an independent cohort. Subnetwork analysis of the 10 proteins from the regression analysis identified the ontological theme, with the strongest associations being with acute phase and acute inflammatory responses.
Conclusion This longitudinal study of 180 patients with RA commencing etanercept has identified several putative protein biomarkers of treatment response to this drug, one of which was replicated in an independent cohort.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Ⓒ The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | RA; biologics; anti-TNF; etanercept; treatment response; proteomics; genetics; biomarkers |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number NIHR National Inst Health Research NIHR202395 NIHR National Inst Health Research BRC MRC (Medical Research Council) R116825 |
Depositing User: | Symplectic Publications |
Date Deposited: | 06 Dec 2023 12:20 |
Last Modified: | 06 Dec 2023 12:20 |
Status: | Published online |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/rheumatology/kead321 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:206190 |