ArticleRMD open2023
Anti-topoisomerase, but not anti-centromere B cell responses in systemic sclerosis display active, Ig-secreting cells associated with lung fibrosis.
Article in RMD open, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Risk factors for pulmonary complications in systemic lupus erythematosus: a meta-analysis of infectious pneumonia and interstitial lung disease.Frontiers in immunology · 2026Pooled it
- Anti-centromere antibody positivity: a spectrum of clinical diagnoses and immunological patterns in a large patient cohort.Clinical rheumatology · 2026Article
- Novel HLA class I and II insights into the pathogenesis of systemic sclerosis-associated interstitial lung disease.Annals of the rheumatic diseases · 2026Article
- Fibrotic Disease of the Skin and Lung: Shared Pathways, Environmental Drivers, and Therapeutic Opportunities in a Changing Climate.International journal of molecular sciences · 2025Review
- Absence of Functional Autoantibodies Targeting Angiotensin II Receptor Type 1 and Endothelin-1 Type A Receptor in Circulation and Purified IgG From Patients With Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Treating connective tissue disease-associated interstitial lung disease - think outside the box: a perspective.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Autoantibodies in systemic sclerosis: From disease bystanders to pathogenic players.Journal of translational autoimmunity · 2025Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesAlmost all patients with systemic sclerosis (SSc) harbour autoantibodies. Anti-topoisomerase antibodies (ATA) and anti-centromere antibodies (ACA) are most prevalent and associate with distinct clinical phenotypes. B cell responses underlying these phenotypes are ill-defined. To understand how B cell autoreactivity and disease pathology connect, we determined phenotypic and functional characteristics of autoreactive B cells in ATA-positive and ACA-positive patients.
methodsLevels and isotypes of autoantibodies secreted by ex vivo cultured peripheral blood mononuclear cells from patients with ATA-positive (n=22) and ACA-positive (n=20) SSc were determined. Antibody secreting cells (ASCs) were isolated by cell sorting and cultured separately. Correlations were studied between the degree of spontaneous autoantibody production and the presence and degree of interstitial lung disease (ILD).
resultsCirculating B cells secreting either ATA-immunoglobulin G (IgG) or ACA-IgG on stimulation was readily detectable in patients. The ATA response, but not the ACA response, showed additional secretion of autoreactive IgA. ATA-IgG and ATA-IgA were also secreted spontaneously. Additional cell sorting confirmed the presence of ATA-secreting plasmablasts. The degree of spontaneous ATA-secretion was higher in patients with ILD than in those without (p<0.001) and correlated with the degree of pulmonary fibrosis (p<0.001).
conclusionIn contrast to ACA-positive patients, ATA-positive patients show signs of recent activation of the B cell response that hallmarks this disease. The degree of activation correlates with the presence and severity of ILD, the most deleterious disease manifestation. This could explain differential responsiveness to B cell depleting therapy. The abundant and spontaneous secretion of ATA-IgG and ATA-IgA may point toward a continuously activating trigger.
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