ArticleArthritis & rheumatology (Hoboken, N.J.)2022
Variability of Primary Sjögren's Syndrome Is Driven by Interferon-α and Interferon-α Blood Levels Are Associated With the Class II HLA-DQ Locus.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- [Epidemiology and manifestations of Sjögren's disease].Zeitschrift fur Rheumatologie · 2026Article
- The SjD Map: an interactive pathway tour into Sjögren's disease signalling mechanisms.NPJ systems biology and applications · 2026Article
- Update on the Aetiopathogenesis of Sjögren Disease: From Interferon Signaling to Epithelial Dysfunction.Journal of clinical medicine · 2026Review
- [Interferon scores in the management of rheumatic systemic diseases].Zeitschrift fur Rheumatologie · 2026Review
- Sjögren's disease metabolome reveals biomarker signatures to characterise patients and assess disease activity.RMD open · 2026Article
- Imbalance of type I and II interferon pathways is associated with pain perception in Sjogren's disease: a real-life study.Frontiers in immunology · 2026Article
- Immunological profiling of rheumatoid factor-positive primary Sjögren's syndrome by single-cell RNA sequencing.Frontiers in immunology · 2026Article
- Genome-wide gene expression analysis suggests an important regulatory role of lncRNAs in primary Sjögren's syndrome.Frontiers in immunology · 2026Article
- Predicted T-Cell and B-Cell Epitopes of NIS: Where Do Sjögren's Syndrome and Hashimoto's Thyroiditis Converge?International journal of molecular sciences · 2025Article
- Reduced HBsAg positivity in systemic lupus erythematosus and Sjögren's syndrome: A retrospective comparative study.Biochemistry and biophysics reports · 2025Article
- Ultrasensitive Test Systems Are Required to Quantify Interferon Alpha Protein in Serum Samples.European journal of immunology · 2025Article
- Mutually reinforcing relationship between Sjögren's syndrome and lung adenocarcinoma: insights from Mendelian randomisation, single-cell, and transcriptomic analyses.Frontiers of medicine · 2025Article
- HLA loci heterozygosity modulates genetic risk in idiopathic inflammatory myopathies.Annals of the rheumatic diseases · 2025Article
- Insights into Patient Heterogeneity in Sjögren's Disease.International journal of molecular sciences · 2025Review
- Sjögren's Syndrome: Epidemiology, Classification Criteria, Molecular Pathogenesis, Diagnosis, and Treatment.MedComm · 2025Review
- Psoriasis increases the risk of Sjögren's syndrome: evidence from a propensity score-matched cohort study and transcriptomic analysis.BMC medicine · 2025Article
- Salivary gland transcriptomic analysis and immunophenotyping in the IL-14α transgenic mouse model of Sjögren's disease.Frontiers in dental medicine · 2025Article
- Revisiting the heterogeneity of interferon-related autoimmune diseases.Nature reviews. Rheumatology · 2025Article
- Loss of tolerance precedes triggering and lifelong persistence of pathogenic type I interferon autoantibodies.The Journal of experimental medicine · 2024Article
- Role of mucosal-associated invariant T cells dynamics in pathogenesis of Sjögren syndrome.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
26 authors at 12 institutions in 6 countries.
Funding
Abstract
objectivePrimary Sjögren's syndrome (SS) is the second most frequent systemic autoimmune disease, affecting 0.1% of the general population. To characterize the molecular and clinical variabilities among patients with primary SS, we integrated transcriptomic, proteomic, cellular, and genetic data with clinical phenotypes in a cohort of 351 patients with primary SS.
methodsWe analyzed blood transcriptomes and genotypes of 351 patients with primary SS who were participants in a multicenter prospective clinical cohort. We replicated the transcriptome analysis in 3 independent cohorts (n = 462 patients). We determined circulating interferon-α (IFNα) and IFNγ protein concentrations using digital single molecular arrays (Simoa).
resultsTranscriptome analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients; this finding was replicated in the 3 independent cohorts. Because gene expression analysis did not discriminate between type I IFN and type II IFN, we used Simoa to demonstrate that the IFN transcriptomic signature was driven by circulating IFNα and not by IFNγ protein levels. IFNα protein levels, detectable in 75% of patients, were significantly associated with clinical and immunologic features of primary SS disease activity at enrollment and with increased frequency of systemic complications over the 5-year follow-up. Genetic analysis revealed a significant association between IFNα protein levels, a major histocompatibility (MHC) class II haplotype, and anti-SSA antibody. Additional cellular analysis revealed that an MHC class II HLA-DQ locus acts through up-regulation of HLA class II molecules on conventional dendritic cells.
conclusionWe identified the predominance of IFNα as a driver of primary SS variability, with IFNα demonstrating an association with HLA gene polymorphisms.
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Registered trials
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