ArticleArthritis research & therapy2016
Antibodies directed against endogenous and exogenous citrullinated antigens pre-date the onset of rheumatoid arthritis.
Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- 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
- Protective and Pathogenic Antibodies to Citrullinated Antigens.Immunological reviews · 2026Review
- Decoding the association between microorganisms and autoimmunity: a multifaceted review of evidence on specific pathogens that trigger autoimmune diseases.Clinical and experimental medicine · 2026Review
- Detection of Diagnostic Antibodies in Immune-Mediated Diseases: A Focus on Antigens and Technologies.Chembiochem : a European journal of chemical biology · 2026Review
- Macrophage-centred crosstalk with infiltrating immune cells in rheumatoid arthritis and its regulation by mesenchymal stem cells.Journal of translational medicine · 2025Review
- Cytokines, chemokines and antibodies against histone-3/4 citrullinated peptides in rheumatoid arthritis patients with pulmonary fibrosis.Arthritis research & therapy · 2025Article
- Citrullinated peptides as drug candidates for rheumatoid arthritis.Frontiers in immunology · 2025Review
- Review
- Recent advances in characterization of citrullination and its implication in human disease research: From method development to network integration.Proteomics · 2023Review
- Aberrant Activation of Immune and Non-Immune Cells Contributes to Joint Inflammation and Bone Degradation in Rheumatoid Arthritis.International journal of molecular sciences · 2023Review
- Epstein-Barr virus infection: the micro and macro worlds.Virology journal · 2023Review
- Platelets derived citrullinated proteins and microparticles are potential autoantibodies ACPA targets in RA patients.Frontiers in immunology · 2023Article
- Mechanism-driven strategies for prevention of rheumatoid arthritis.Rheumatology & autoimmunity · 2022Article
- Antibody Responses to Epstein-Barr Virus in the Preclinical Period of Rheumatoid Arthritis Suggest the Presence of Increased Viral Reactivation Cycles.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- LC-MS/MS-Based Serum Protein Profiling for Identification of Candidate Biomarkers in Pakistani Rheumatoid Arthritis Patients.Life (Basel, Switzerland) · 2022Article
- Genetics of rheumatoid arthritis.Seminars in immunopathology · 2022Review
- Impact of Posttranslational Modification in Pathogenesis of Rheumatoid Arthritis: Focusing on Citrullination, Carbamylation, and Acetylation.International journal of molecular sciences · 2021Review
- Adiponectin Associates with Rheumatoid Arthritis Risk in Overweight and Obesity Independently of Other Adipokines.Journal of clinical medicine · 2021Article
- Elevated Anti-Citrullinated Protein Antibodies Prior to Rheumatoid Arthritis Diagnosis and Risks for Chronic Obstructive Pulmonary Disease or Asthma.Arthritis care & research · 2021Article
- Adipocytokines in Untreated Newly Diagnosed Rheumatoid Arthritis: Association with Circulating Chemokines and Markers of Inflammation.Biomolecules · 2021Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAnti-citrullinated-peptide antibodies (ACPA) have been detected in individuals with developing rheumatoid arthritis (RA) before the onset of symptom, with an initially limited spectrum of reactivities that gradually broadens. The aim was to analyze the evolution of ACPA response pre-dating symptom onset, using four selected citrullinated exogenous and endogenous antigens.
methodsA cohort of 521 individuals sampled before symptoms of RA appeared and 272 population controls were identified from the Biobank of Northern Sweden; 241 samples from patients with early RA were also collected. ACPA were detected by ELISA on viral citrullinated peptides (VCP) derived from Epstein-Barr-virus nuclear antigen (EBNA)1 and EBNA2 (VCP1 and VCP2) and histone-4-derived citrullinated peptides (HCP1 and HCP2).
resultsIn pre-symptomatic individuals vs. patients with early RA, anti-VCP1 antibodies were detected in 10.4 % vs. 36.1 %, anti-VCP2 in 17.1 % vs. 52.3 %, anti-HCP1 in 10.2 % vs. 37.3 %, and anti-HCP2 in 16.3 % vs. 48.5 %, respectively. Anti-VCP and anti-HCP concentrations were significantly increased in pre-symptomatic individuals vs. controls (p < 0.001) and were increased approaching symptom onset. Anti-VCP and anti-HCP appeared simultaneously (median (IQR) 5.3 (6) years before symptom onset) and in combination yielded a high-risk ratio for disease development (OR = 8.0-18.9). Anti-VCP2 and anti-HCP2 antibodies were associated with HLA-DRB1*0401 in pre-symptomatic individuals. Three peptidylarginine deiminase (PAD)I3/PADI4 single nucleotide polymorphisms (SNPs) were significantly associated with anti-HCP1.
conclusionsAnti-VCP and anti-HCP antibodies pre-date symptom onset and predict disease development, but no hierarchy of citrullinated epitopes can be identified. These results suggest that no inciting citrullinated antigen so far described is common to all patients with RA. The association between PADI3/PADI4 polymorphism and anti-HCP1 antibodies suggests a novel link between deimination and production of ACPA.
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