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Lookup NU author(s): Professor John IsaacsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2023. 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 g 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.
Author(s): Ling SF, Yap CF, Nair N, Bluett J, Morgan AW, Isaacs JD, Wilson AG, Hyrich KL, Barton A, Plant D
Publication type: Article
Publication status: Published
Journal: Rheumatology
Year: 2024
Volume: 63
Issue: 4
Pages: 1015-1021
Print publication date: 01/04/2024
Online publication date: 30/06/2023
Acceptance date: 15/06/2023
Date deposited: 17/04/2024
ISSN (print): 1462-0324
ISSN (electronic): 1462-0332
Publisher: Oxford University Press
URL: https://doi.org/10.1093/rheumatology/kead321
DOI: 10.1093/rheumatology/kead321
Data Access Statement: Data are available upon request to the corresponding author.
PubMed id: 37389432
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