ArticleArthritis & rheumatology (Hoboken, N.J.)2022
Association of Sputum Neutrophil Extracellular Trap Subsets With IgA Anti-Citrullinated Protein Antibodies in Subjects at Risk for Rheumatoid Arthritis.
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 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Adventitial root extract of oplopanax elatus alleviates rheumatoid arthritis via inhibiting NETosis.Clinical rheumatology · 2026Article
- The evolving landscape of complement therapeutics in rheumatology.Annals of the rheumatic diseases · 2026Review
- Susceptibility to systemic autoimmunity rather than the presence of the HLA-DR4 peptide binding domain alone leads to severe inflammatory arthritis following inhalation of crystalline silica.Particle and fibre toxicology · 2026Article
- Anti-cyclic citrullinated peptide antibody in bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis.BMC pulmonary medicine · 2026Article
- Neutrophil extracellular traps in rheumatoid arthritis: biomarkers, drivers, and emerging therapeutic targets.Clinical and experimental immunology · 2026Review
- Catalpol mitigates rheumatoid arthritis by targeting neutrophil extracellular trap release.Frontiers in immunology · 2026Article
- Rheumatoid factor and anti-citrullinated protein IgA antibodies in the diagnosis, prognosis and monitoring of patients with rheumatoid arthritis.Journal of translational autoimmunity · 2025Review
- Advances in Drug Research Targeting Neutrophils for the Treatment of Rheumatoid Arthritis.Current rheumatology reports · 2025Review
- A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis.Nature communications · 2025Article
- Review
- Proteasome Inhibitors: Potential in Rheumatoid Arthritis Therapy?International journal of molecular sciences · 2025Review
- Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis.The Journal of clinical investigation · 2025Article
- Neutrophil extracellular traps - an a-list-actor in a variety of diseases.Annals of hematology · 2024Review
- Distinct mucosal endotypes as initiators and drivers of rheumatoid arthritis.Nature reviews. Rheumatology · 2024Review
- Screening, diagnosis, and monitoring of interstitial lung disease in autoimmune rheumatic diseases: A narrative review.Revista colombiana de reumatologia · 2024Article
- The emerging role of neutrophil extracellular traps in the progression of rheumatoid arthritis.Frontiers in immunology · 2024Review
- Ginger intake suppresses neutrophil extracellular trap formation in autoimmune mice and healthy humans.JCI insight · 2023Article
- The role of neutrophil extracellular traps and proinflammatory damage-associated molecular patterns in idiopathic inflammatory myopathies.Clinical and experimental immunology · 2023Article
- Prediction of Erosive Disease Development by Antimitochondrial Antibodies in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Anti-Citrullinated Protein Antibody Reactivity towards Neutrophil-Derived Antigens: Clonal Diversity and Inter-Individual Variation.Biomolecules · 2023Article
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Authors and funding
23 authors at 5 institutions in 2 countries.
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Abstract
objectiveMechanisms leading to anti-citrullinated protein antibody (ACPA) generation in rheumatoid arthritis (RA) are hypothesized to originate in the lung. We undertook this study to understand associations between neutrophil extracellular trap (NET) formation in the lung and local ACPA generation in subjects at risk of developing RA.
methodsInduced sputum was collected from 49 subjects at risk of developing RA, 12 patients with RA, and 18 controls. Sputum neutrophils were tested for ex vivo NET formation, and sputum-induced NET formation of control neutrophils was measured using immunofluorescence imaging. Sputum macrophages were tested for ex vivo endocytosis of apoptotic and opsonized cells. Levels of ACPA, NET remnants, and inflammatory proteins were quantified in sputum supernatant.
resultsSpontaneous citrullinated histone H3 (Cit-H3)-expressing NET formation was higher in sputum neutrophils from at-risk subjects and RA patients compared to controls (median 12%, 22%, and 0%, respectively; P < 0.01). In at-risk subjects, sputum IgA ACPA correlated with the percentage of neutrophils that underwent Cit-H3+ NET formation (r = 0.49, P = 0.002) and levels of Cit-H3+ NET remnants (r = 0.70, P < 0.001). Reduced endocytic capacity of sputum macrophages was found in at-risk subjects and RA patients compared to controls. Using a mediation model, we found that sputum inflammatory proteins were associated with sputum IgA ACPA through a pathway mediated by Cit-H3+ NET remnants. Sputum-induced Cit-H3+ NET formation also correlated with sputum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor in at-risk subjects, suggesting a causal relationship.
conclusionThese data support a potential mechanism for mucosal ACPA generation in subjects at risk of developing RA, whereby inflammation leads to increased citrullinated protein-expressing NETs that promote local ACPA generation.
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