ArticleAnnals of the rheumatic diseases2022
Interferon-α-mediated therapeutic resistance in early rheumatoid arthritis implicates epigenetic reprogramming.
Article in Annals of the rheumatic diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- Ozoralizumab shows effectiveness regardless of baseline RF and ACPA titres in patients with RA: a post hoc analysis of the OHZORA trial.Rheumatology (Oxford, England) · 2025Trial
- BCAT2 links branched-chain amino acids metabolism to interferon signaling to sustain macrophage inflammation.Nature immunology · 2026Article
- Interferon-Mediated Regulation of Memory B Cell Identity and Function.Immunological reviews · 2026Review
- cellGeometry: ultra-fast single-cell deconvolution of bulk RNA-Seq using a geometric solution.Nature communications · 2026Article
- Ganoderma lucidum spore powder enhances IFN-α-mediated antiviral capacity of COVID-19 vaccine boosters revealed by single-cell multi-omics sequencing.Journal of advanced research · 2026Article
- Review
- [Interferon scores in the management of rheumatic systemic diseases].Zeitschrift fur Rheumatologie · 2026Review
- Factors Associated with Difficult-to-Treat Rheumatoid Arthritis (D2T-RA): Real-World Evidence from a Single-Center Cross-Sectional Study.Journal of personalized medicine · 2026Article
- IFI44L modulates chemoradiotherapy sensitivity and CD8Frontiers in oncology · 2026Article
- The Type I Interferon Axis in Systemic Autoimmune Diseases: From Molecular Pathways to Targeted Therapy.Biomolecules · 2025Review
- Article
- Endogenous Retroelement Activation is Implicated in Interferon-α Production and Anti-Cyclic Citrullinated Peptide Autoantibody Generation in Early Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Aquaporin‑1 regulates microglial polarization and inflammatory response in traumatic brain injury.International journal of molecular medicine · 2025Article
- Rheumatoid Factor: Diagnostic and Prognostic Performance and Therapeutic Implications in Rheumatoid Arthritis.Journal of clinical medicine · 2025Review
- DualFrontiers in immunology · 2025Article
- Thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus after anifrolumab: a possible association.Archive of clinical cases · 2025Article
- Integrative multi-omics analysis reveals the interaction mechanisms between gut microbiota metabolites and ferroptosis in rheumatoid arthritis.Frontiers in immunology · 2025Article
- Unmet Needs and Current Challenges of Rheumatoid Arthritis: Difficult-to-Treat Rheumatoid Arthritis and Late-Onset Rheumatoid Arthritis.Journal of clinical medicine · 2024Review
- Identification of NET formation and the renoprotective effect of degraded NETs in lupus nephritis.American journal of physiology. Renal physiology · 2024Article
- A roadmap to the molecular human linking multiomics with population traits and diabetes subtypes.Nature communications · 2024Article
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
Abstract
objectivesAn interferon (IFN) gene signature (IGS) is present in approximately 50% of early, treatment naive rheumatoid arthritis (eRA) patients where it has been shown to negatively impact initial response to treatment. We wished to validate this effect and explore potential mechanisms of action.
methodsIn a multicentre inception cohort of eRA patients (n=191), we examined the whole blood IGS (
resultsWe reproduced our previous findings demonstrating a raised baseline IGS. We additionally showed, for the first time, that the IGS in eRA reflects circulating IFN-α protein. Paired longitudinal analysis demonstrated a significant reduction between baseline and 6-month IGS and IFN-α levels (p<0.0001 for both). Despite this fall, a raised baseline IGS predicted worse 6-month clinical outcomes such as increased disease activity score (DAS-28, p=0.025) and lower likelihood of a good EULAR clinical response (p=0.034), which was independent of other conventional predictors of disease activity and clinical response. Molecular analysis of CD4+ T cells and CD19+ B cells demonstrated differentially methylated CPG sites and dysregulated expression of disease relevant genes, including
conclusionsOur data suggest that, in eRA, IFN-α can cause a sustained, epigenetically mediated, pathogenic increase in lymphocyte activation and proliferation, and that the IGS is, therefore, a robust prognostic biomarker. Its persistent harmful effects provide a rationale for the initial therapeutic targeting of IFN-α in selected patients with eRA.
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