ArticleAnnals of the rheumatic diseases2016
Single cell cloning and recombinant monoclonal antibodies generation from RA synovial B cells reveal frequent targeting of citrullinated histones of NETs.
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. It is linked to trial NCT04474392 (Sputum Studies of Anti-Citrullinated Protein Antibodies), which is not on this map. Cited by 115 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
115 citing papers in PubMed, 2 syntheses or guidelines pooled it, 188 citations in OpenAlex.
- Global research landscape and emerging trends of tertiary lymphoid structures in autoimmune diseases: a bibliometric analysis.Frontiers in immunology · 2026Pooled it
- In vitro induction of NETosis: Comprehensive live imaging comparison and systematic review.PloS one · 2017Pooled it
- Characterization of Phenotypes and Functional Activities of Leukocytes From Rheumatoid Arthritis Patients by Mass Cytometry.Frontiers in immunology · 2019Trial
- Neutrophil Extracellular Traps in the Tumor Microenvironment: Mechanisms, Immune Regulation, and Implications for Immune Checkpoint Inhibitor Therapy.International journal of molecular sciences · 2026Review
- Anti-Modified Protein Antibodies in Rheumatoid Arthritis: Pathogenic, Protective, or Passive Bystander?Immunological reviews · 2026Review
- Cross-presentation of citrullinated antigens drives cytotoxic CD8bioRxiv : the preprint server for biology · 2026Article
- Inflammation-Driven Lymphoid Structures: Organization, Function, and Clinical Impact Across Autoimmunity, Cancer, and Checkpoint Toxicity.Immunological reviews · 2026Review
- Proceedings of the 2Mediterranean journal of rheumatology · 2026Article
- Integrative multi-omics analysis reveals CXCL10-driven inflammation and TREM2 + macrophage-plasma cell survival niche as hallmarks of late-stage rheumatoid arthritis.Arthritis research & therapy · 2026Article
- Plasmablasts as Translational Biomarkers in Autoimmune Diseases: From Cellular Dynamics to Clinical Decision-Making.Current issues in molecular biology · 2026Review
- Interactions between neutrophil extracellular traps and macrophages: the key to inflammatory diseases.Frontiers in immunology · 2026Review
- Revisiting B-cell targeted therapies in rheumatoid arthritis: from paradoxical biology to deep immune reset.Frontiers in immunology · 2026Review
- Single-cell analysis of B cell dysregulation in pediatric sepsis stratified by disease severity.Scientific reports · 2025Observational
- Rituximab in Connective Tissue Disease-Associated Interstitial Lung Disease: From Immunopathogenesis to Therapeutic Implications.International journal of molecular sciences · 2025Review
- Joint Tissues: Convergence and Divergence of the Pathogenetic Mechanisms of Rheumatoid Arthritis and Osteoarthritis.International journal of molecular sciences · 2025Review
- Neutrophil Extracellular Traps in Cardiovascular Diseases: Pathological Roles and Therapeutic Implications.Biomolecules · 2025Review
- Naive and Memory B Cell BCR Repertoires in Individuals Immunized with an Inactivated SARS-CoV-2 Vaccine.Vaccines · 2025Article
- The emerging role of neutrophil extracellular traps in autoimmune and autoinflammatory diseases.MedComm · 2025Review
- Deep topic modeling of spatial transcriptomics in the rheumatoid arthritis synovium identifies distinct classes of ectopic lymphoid structures.bioRxiv : the preprint server for biology · 2025Article
- NETs: a new target for autoimmune disease.Frontiers in immunology · 2025Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
objectivesRheumatoid arthritis (RA) is characterised by breach of self-tolerance towards citrullinated antigens with generation of anti-citrullinated peptide/proteins antibodies (ACPA). Currently, the nature and source of citrullinated antigens driving the humoral autoimmune response within synovial ectopic lymphoid structures (ELS) is a crucial unknown aspect of RA pathogenesis. Here we characterised the autoreactive B-cell response of lesional B cells isolated from ELS+RA synovium.
methodsSingle synovial tissue CD19+cells were Fluorescence Activated Cell Sorting (FACS)-sorted and VH/VL Ig genes cloned to generate recombinant monoclonal antibodies (rmAbs) from patients with ELS+/ACPA+RA.
resultsRA-rmAbs immunoreactivity analysis provided the following key findings: (1) in a chIP-based array containing 300 autoantigens and in a 'citrullinome' multiplex assay, a strong reactivity against citrullinated histones H2A/H2B (citH2A/H2B) was observed in ∼40% of RA-rmAbs, followed by cit-fibrinogen and cit-vimentin; (2) anti-citH2A/H2B-reactive RA-rmAbs (but not anti-citH2A/H2B negative) selectively recognised neutrophil extracellular traps (NETs) from peripheral blood and/or RA joint neutrophils; (3) anti-citH2A/citH2B and anti-NET immunobinding was dependent on affinity maturation and was completely abrogated following reversion of hypermutated IgVH/VL genes to germline sequences; (4) ELS+ (not ELS-) RA synovial tissues engrafted into Severe Combined ImmunoDeficiency (SCID) mice released human anti-citH2A/citH2B and anti-NET antibodies in association with the intra-graft expression of CXCL13 and lymphotoxin (LT)-β, two master regulators of ELS.
conclusionWe provided novel evidence that B cells differentiated within synovial ELS in the RA joints frequent target deiminated proteins which could be generated during NETosis of RA synovial neutrophils including histones. Thus, NETs could represent a source of citrullinated antigens fuelling the ACPA autoimmune response within the RA synovium.
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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.