ArticleRheumatology (Oxford, England)2021
Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome.
Article in Rheumatology (Oxford, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Sjögren's syndrome: novel insights from proteomics and miRNA expression analysis.Frontiers in immunology · 2023Pooled it
- Low albumin-to-globulin ratio is associated with interstitial lung disease in primary Sjögren's syndrome: a single-center retrospective cohort study with propensity score matching.Rheumatology international · 2026Article
- Data-driven classification of primary Sjögren's syndrome: From cluster analysis to clinical immune phenotypes and predictive biomarkers.Journal of translational autoimmunity · 2026Article
- Decreased Serum Vitamin D Is Not Associated With Sjögren Disease in European and Asian Subjects.ACR open rheumatology · 2026Article
- Cracking the Code: Which Ocular Symptoms Predict Dry Eye Signs? Insights From a Large International Sicca Registry.Arthritis care & research · 2026Article
- The power of genetics in decoding Sjögren's disease: current status and future development.Current opinion in immunology · 2026Review
- Spatiotemporal orchestration of the salivary gland immune microenvironment in Sjögren's disease: a multidimensional framework of epithelial licensing, lymphoid neogenesis, and stromal remodeling.Frontiers in immunology · 2026Review
- Characterization of Peripheral Blood Immune Cell Features in SSA/SSB Double‑Positive Primary Sjögren's Disease Based on Single‑Cell RNA Sequencing.Journal of inflammation research · 2026Article
- Immunophenotypic Stratification of Primary Sjögren's Syndrome Reveals Distinct Lymphocyte Profiles and Clinical Manifestations.Journal of immunology research · 2026Article
- A high polygenic risk score is associated with SSA/SSB antibody positivity and early onset in primary Sjögren's disease.Rheumatology (Oxford, England) · 2025Article
- Post-genome-wide association study dissects genetic vulnerability and risk gene expression of Sjögren's disease for cardiovascular disease.Journal of translational medicine · 2025Article
- Conjunctival MicroRNA Expression Signature in Primary Sjögren's Syndrome Dry Eye: A NanoString-Based Bioinformatic Analysis.Investigative ophthalmology & visual science · 2025Article
- Unraveling the Genetics of Shared Clinical and Serological Manifestations in Patients With Systemic Inflammatory Autoimmune Diseases.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- An overview on Sjögren's syndrome and systemic lupus erythematosus' genetics.Toxicology research · 2025Review
- Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders.Signal transduction and targeted therapy · 2024Review
- HLA-DR genotypes in patients with primary Sjögren's syndrome in Taiwan.The Kaohsiung journal of medical sciences · 2024Article
- Patients' recollection about the onset of Sjögren's disease - a mixed methods study on the patients' perspective.Arthritis research & therapy · 2024Article
- Vitamin D in Primary Sjogren's Syndrome (pSS) and the Identification of Novel Single-Nucleotide Polymorphisms Involved in the Development of pSS-Associated Diseases.Diagnostics (Basel, Switzerland) · 2024Review
- Seronegative primary Sjögren's syndrome, a distinct subtype of primary Sjögren's syndrome in Chinese patients.BMC rheumatology · 2024Article
- CXCL9 may serve as a potential biomarker for primary Sjögren's syndrome with extra-glandular manifestations.Arthritis research & therapy · 2024Article
Corrections and comments
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Authors and funding
33 authors at 15 institutions in 4 countries.
Funding
Abstract
objectivesClinical presentation of primary Sjögren's syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints.
methodsWe performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls.
resultsWe found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10-62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS.
conclusionTwo subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.
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