ArticleArthritis & rheumatology (Hoboken, N.J.)2017
Anti-Citrullinated Protein Antibodies Are Associated With Neutrophil Extracellular Traps in the Sputum in Relatives of Rheumatoid Arthritis Patients.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04474392 (Sputum Studies of Anti-Citrullinated Protein Antibodies), which is not on this map. Cited by 85 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Sputum Studies of Anti-Citrullinated Protein Antibodies (ACPA) and Rheumatoid Arthritis (RA) Origins
Who cites it
85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis.Annals of the rheumatic diseases · 2021Guideline
- Role of Neutrophils on the Ocular Surface.International journal of molecular sciences · 2021Pooled it
- A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and interstitial lung disease in systemic sclerosis.Scientific reports · 2022Trial
- Targeting peptidyl-arginine deiminase 4 suppresses SARS-CoV-2 replication and modulates the inflammatory response.iScience · 2026Article
- Neutrophil degranulation in the lung microenvironment linked to idiopathic pulmonary fibrosis severity and survival.iScience · 2026Article
- Autophagy in Rheumatoid Arthritis: Molecular Mechanisms, Diagnostic Biomarkers, and Emerging Therapeutic Strategies.Inflammation · 2026Review
- Neutrophil extracellular traps in rheumatoid arthritis: biomarkers, drivers, and emerging therapeutic targets.Clinical and experimental immunology · 2026Review
- Association Between Neutrophil Percentage to Albumin Ratio and Disease Activity in Hospitalized Patients with Rheumatoid Arthritis: A Cross-Sectional Study.Journal of inflammation research · 2026Article
- A large-scale profiling study of immune-coagulation associations in rheumatoid arthritis.Frontiers in immunology · 2026Article
- Systemic neutrophil activation and N-formyl methionine-formyl peptide receptor-1 signaling define inflammatory endotypes in rheumatoid arthritis-associated lung involvement.Journal of internal medicine · 2025Article
- Rheumatoid factor and anti-citrullinated protein IgA antibodies in the diagnosis, prognosis and monitoring of patients with rheumatoid arthritis.Journal of translational autoimmunity · 2025Review
- Transforming growth factor-beta is increased in sputum from individuals with rheumatoid arthritis-associated pulmonary fibrosis.Rheumatology (Oxford, England) · 2025Article
- Evidence of Site-Specific Mucosal Autoantibody Secretion in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Biological mechanisms of pulmonary inflammation and its association with seropositive rheumatoid arthritis.Frontiers in immunology · 2025Review
- Citrullinated peptides as drug candidates for rheumatoid arthritis.Frontiers in immunology · 2025Review
- Restoring immune tolerance in pre-RA: immunometabolic dialogue between gut microbiota and regulatory T cells.Frontiers in immunology · 2025Review
- Distinct mucosal endotypes as initiators and drivers of rheumatoid arthritis.Nature reviews. Rheumatology · 2024Review
- Article
- The peculiar features, diversity and impact of citrulline-reactive autoantibodies.Nature reviews. Rheumatology · 2024Review
- Neutrophil extracellular traps linked to idiopathic pulmonary fibrosis severity and survival.medRxiv : the preprint server for health sciences · 2024Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 1 country.
Funding
Abstract
objectiveStudies suggest that rheumatoid arthritis (RA)-related autoimmunity is initiated at a mucosal site. However, the factors associated with the mucosal generation of this autoimmunity are unknown, especially in individuals who are at risk of future RA. Therefore, we tested anti-cyclic citrullinated peptide (anti-CCP) antibodies in the sputum of RA-free first-degree relatives (FDRs) of RA patients and patients with classifiable RA.
methodsWe evaluated induced sputum and serum samples from 67 FDRs and 20 RA patients for IgA anti-CCP and IgG anti-CCP, with cutoff levels for positivity determined in a control population. Sputum was also evaluated for cell counts, neutrophil extracellular traps (NETs) using sandwich enzyme-linked immunosorbent assays for protein/nucleic acid complexes, and total citrulline.
resultsSputum was positive for IgA and/or IgG anti-CCP in 14 of 20 RA patients (70%) and 17 of 67 FDRs (25%), including a portion of FDRs who were serum anti-CCP negative. In the FDRs, elevations of sputum IgA and IgG anti-CCP were associated with elevated sputum cell counts and NET levels. IgA anti-CCP was associated with ever smoking and with elevated sputum citrulline levels.
conclusionAnti-CCP is elevated in the sputum of FDRs, including seronegative FDRs, suggesting that the lung may be a site of anti-CCP generation in this population. The association of anti-CCP with elevated cell counts and NET levels in FDRs supports a hypothesis that local airway inflammation and NET formation may drive anti-CCP production in the lung and may promote the early stages of RA development. Longitudinal studies are needed to follow the evolution of these processes relative to the development of systemic autoimmunity and articular RA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.