ArticleAnnals of the rheumatic diseases2016
Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss.
Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04474392 (Sputum Studies of Anti-Citrullinated Protein Antibodies), which is not on this map. Cited by 179 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
179 citing papers in PubMed, 2 syntheses or guidelines pooled it, 338 citations in OpenAlex.
- Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis.Frontiers in immunology · 2022Pooled it
- Fc Gamma Receptors as Regulators of Bone Destruction in Inflammatory Arthritis.Frontiers in immunology · 2021Pooled it
- The role of anti-citrullinated protein antibody reactivities in an inception cohort of patients with rheumatoid arthritis receiving treat-to-target therapy.Arthritis research & therapy · 2018Trial
- Anti-Modified Protein Antibodies in Rheumatoid Arthritis: Pathogenic, Protective, or Passive Bystander?Immunological reviews · 2026Review
- Absence of osteoclastogenic response to pooled polyclonal anti-citrullinated peptide/protein antibodies from patients with rheumatoid arthritis in vitro.Clinical and experimental medicine · 2026Article
- Osteoimmunology: Can We Prevent Bone Loss in Rheumatoid Arthritis with Modern Antirheumatic Drugs?Calcified tissue international · 2026Review
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- TNF-α blockade with adalimumab restores bone metabolism in rheumatoid arthritis by regulating cytokines and inflammatory cell infiltration.Frontiers in immunology · 2026Article
- Failed resolution as a mechanistic basis of difficult-to-treat rheumatoid arthritis: stromal-myeloid crosstalk in the synovium and emerging resolution-restoring therapies.Frontiers in immunology · 2026Review
- Presence and reactivities of antibodies directed to citrullinated peptides in a Swedish JIA cohort.Pediatric rheumatology online journal · 2025Article
- Joint Tissues: Convergence and Divergence of the Pathogenetic Mechanisms of Rheumatoid Arthritis and Osteoarthritis.International journal of molecular sciences · 2025Review
- Multi-target drug discovery for rheumatoid arthritis: a comprehensive computational approach using bioactive compounds.Scientific reports · 2025Article
- CXCL7 enhances RANKL-induced osteoclastogenesis via the activation of ERK/NFATc1 signaling pathway in inflammatory arthritis.Arthritis research & therapy · 2025Article
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- Article
- Nano-based Therapeutics for Rheumatoid Arthritis: Recent Patents and Development.Recent patents on nanotechnology · 2025Review
- Pain mechanism and management strategy of rheumatoid arthritis.Frontiers in pain research (Lausanne, Switzerland) · 2025Review
- Article
- Revisiting the Link Between HLA-DRB1 Alleles and Autoantibodies in Rheumatoid Arthritis: Association of non-Shared Epitope Alleles *09 and *15 With High Levels of Anti-Citrullinated Peptide/Protein Antibodies.ACR open rheumatology · 2025Article
- Identification of early risk factors for anti-citrullinated-protein-antibody positive rheumatoid arthritis-a prospective cohort study.Rheumatology (Oxford, England) · 2024Article
119 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issuedCorrection:2019
Authors and funding
24 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesRheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) appear before disease onset and are associated with bone destruction. We aimed to dissect the role of ACPAs in osteoclast (OC) activation and to identify key cellular mediators in this process.
methodsPolyclonal ACPA were isolated from the synovial fluid (SF) and peripheral blood of patients with RA. Monoclonal ACPAs were isolated from single SF B-cells of patients with RA. OCs were developed from blood cell precursors with or without ACPAs. We analysed expression of citrullinated targets and peptidylarginine deiminases (PAD) enzymes by immunohistochemistry and cell supernatants by cytometric bead array. The effect of an anti-interleukin (IL)-8 neutralising antibody and a pan-PAD inhibitor was tested in the OC cultures. Monoclonal ACPAs were injected into mice and bone structure was analysed by micro-CT before and after CXCR1/2 blocking with reparixin.
resultsProtein citrullination by PADs is essential for OC differentiation. Polyclonal ACPAs enhance OC differentiation through a PAD-dependent IL-8-mediated autocrine loop that is completely abolished by IL-8 neutralisation. Some, but not all, human monoclonal ACPAs derived from single SF B-cells of patients with RA and exhibiting distinct epitope specificities promote OC differentiation in cell cultures. Transfer of the monoclonal ACPAs into mice induced bone loss that was completely reversed by the IL-8 antagonist reparixin.
conclusionsWe provide novel insights into the key role of citrullination and PAD enzymes during OC differentiation and ACPA-induced OC activation. Our findings suggest that IL8-dependent OC activation may constitute an early event in the initiation of the joint specific inflammation in ACPA-positive 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.