ArticleAnnals of the rheumatic diseases2020
Antigen-driven selection of antibodies against SSA, SSB and the centromere 'complex', including a novel antigen, MIS12 complex, in human salivary glands.
Article in Annals of the rheumatic diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Multiple autoantibody-producing B-cell clones coexist within a single human salivary gland.Rheumatology (Oxford, England) · 2026Article
- Identification of a shared antigen linking CD4Science advances · 2026Article
- Identifying the clinical signature of anti-centromere antibody-positive Sjögren's syndrome: a machine learning-based analysis of a multicenter cohort.Frontiers in immunology · 2026Article
- Anti-survival of motor neuron antibodies in rheumatic and musculoskeletal diseases: prevalence, clinical associations, and biomarker potential, with novel insights into disease activity in SLE.Inflammation and regeneration · 2025Article
- Regulatory T cell therapy for Sjögren's disease: From pathogenesis to targeted treatment.Journal of translational autoimmunity · 2025Review
- Pathological Mechanisms in Sjögren's Disease Likely Involve the ADP-Ribosyl Cyclase Family Members: CD38 and CD157.International journal of molecular sciences · 2025Article
- Comparative single-cell and spatial profiling of anti-SSA-positive and anti-centromere-positive Sjögren's disease reveals common and distinct immune activation and fibroblast-mediated inflammation.Nature communications · 2025Article
- Disease-specific autoantibody production in the lungs and salivary glands of anti-synthetase syndrome.Frontiers in immunology · 2024Article
- Annals of the Rheumatic Diseases collection on autoantibodies in the rheumatic diseases: new insights into pathogenesis and the development of novel biomarkers.Annals of the rheumatic diseases · 2023Review
- Current Views on Pathophysiology and Potential Therapeutic Targets in Sjögren's Syndrome: A Review from the Perspective of Viral Infections, Toll-like Receptors, and Long-Noncoding RNAs.Journal of clinical medicine · 2023Review
- Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models.iScience · 2022Article
- Is the anti-centromere antibody a marker for a distinct subset of polyautoimmunity in Sjögren's syndrome?The Korean journal of internal medicine · 2021Article
- Clinical influences of anticentromere antibody on primary Sjögren's syndrome in a prospective Korean cohort.The Korean journal of internal medicine · 2021Article
- Incomplete humoral response including neutralizing antibodies in asymptomatic to mild COVID-19 patients in Japan.Virology · 2021Article
- Immune-Intrinsic Myd88 Directs the Production of Antibodies With Specificity for Extracellular Matrix Components in Primary Sjögren's Syndrome.Frontiers in immunology · 2021Article
- Sjögren's Syndrome: The Clinical Spectrum of Male Patients.Journal of clinical medicine · 2020Article
- Salivary Gland Mucosa-Associated Lymphoid Tissue-Type Lymphoma From Sjögren's Syndrome Patients in the Majority Express Rheumatoid Factors Affinity-Selected for IgG.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesRecent evidences have revealed that anti-SSA/SSB antibodies, the major autoantibodies in Sjögren's syndrome (SS), are produced in salivary glands. This study aims to clarify overall of autoantibody production at lesion site, including anti-centromere antibody (ACA)-positive SS.
methodsAntibodies of antibody-secreting cells in human salivary glands were produced as recombinant antibodies. The reactivity of these antibodies and their revertants were investigated by ELISA and newly developed antigen-binding beads assay, which can detect conformational epitopes. The target of uncharacterised antibodies was identified by immunoprecipitation and mass spectrometry. Autoantibody-secreting cells in salivary gland tissue were identified by immunohistochemistry using green fluorescent protein-autoantigen fusion proteins.
resultsA total of 256 lesion antibodies were generated, and 69 autoantibodies including 24 ACAs were identified among them. Beads assay could detect more autoantibodies than ELISA, suggesting autoantibodies target to antigens with native conformation. After somatic hypermutations were reverted, autoantibodies drastically decreased antigen reactivity. We showed that MIS12 complex, a novel target of ACA, and CENP-C are major targets of ACA produced in salivary glands by examining cloned antibodies and immunohistochemistry, whereas few anti-CENP-B antibodies were detected. The target profiling of serum ACA from 269 patients with SS, systemic sclerosis (SSc), primary biliary cirrhosis (PBC) and healthy controls revealed that ACA-positive patients have antibodies against various sites of centromere complex regardless of disease.
conclusionWe showed direct evidences of antigen-driven maturation of anti-SSA/SSB antibody and ACA in SS lesion. ACA recognises centromere 'complex' rather than individual protein, and this feature is common among patients with SS, SSc and PBC.
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