ArticleArthritis & rheumatology (Hoboken, N.J.)2020
Timing of Elevations of Autoantibody Isotypes Prior to Diagnosis of Rheumatoid Arthritis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 3 of them syntheses that pooled it.
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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.
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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.
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Who cites it
49 citing papers in PubMed, 3 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- Autoantibodies as predictors of progression to rheumatoid arthritis: a systematic review and meta-analysis.RMD open · 2026Pooled it
- The Effects of Periodontal Treatment on Rheumatoid Arthritis and of Anti-Rheumatic Drugs on Periodontitis: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Rheumatoid factor isotypes in rheumatoid arthritis diagnosis and prognosis: a systematic review and meta-analysis.RMD open · 2023Pooled it
- A Phase 2 Trial of Hydroxychloroquine in Individuals at Risk for Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Trial
- Anti-Modified Protein Antibodies in Rheumatoid Arthritis: Pathogenic, Protective, or Passive Bystander?Immunological reviews · 2026Review
- Detecting change-points in preclinical rheumatoid arthritis biomarkers using Bayesian multivariate segmented regression.medRxiv : the preprint server for health sciences · 2026Article
- Longitudinal peripheral blood multi-omic profiling in seropositive individuals identifies immune endotypes and predictive models for future rheumatoid arthritis conversion.medRxiv : the preprint server for health sciences · 2026Article
- Frontiers in Rheumatoid Arthritis: Emerging Research and Unmet Needs in Pharmacologic Management.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Progression to rheumatoid arthritis in at-risk individuals is defined by systemic inflammation and by T and B cell dysregulation.Science translational medicine · 2025Article
- Autoantibody clusters in rheumatoid arthritis are not driven by antigen specificity or isotype.RMD open · 2025Article
- Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis.The Journal of clinical investigation · 2025Article
- Disease activity of rheumatoid arthritis and kidney function decline: a large prospective registry study.Annals of the rheumatic diseases · 2025Article
- Biological mechanisms of pulmonary inflammation and its association with seropositive rheumatoid arthritis.Frontiers in immunology · 2025Review
- Rheumatoid arthritis-associated rheumatoid factors post-COVID-19.Frontiers in immunology · 2025Article
- Systemic inflammation and lymphocyte activation precede rheumatoid arthritis.bioRxiv : the preprint server for biology · 2024Article
- Distinct mucosal endotypes as initiators and drivers of rheumatoid arthritis.Nature reviews. Rheumatology · 2024Review
- Multi-Autoantibody Testing Identifies Expansion of Reactivity to Targeted Antigens Before a Diagnosis of Rheumatoid Arthritis.ACR open rheumatology · 2024Article
- Utility of common investigations for suspected inflammatory arthritis in adults.Australian prescriber · 2024Review
- The role of anti-citrullinated protein antibody in pathogenesis of RA.Clinical and experimental medicine · 2024Review
- The peculiar features, diversity and impact of citrulline-reactive autoantibodies.Nature reviews. Rheumatology · 2024Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveTo evaluate patterns of elevations of isotypes of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) pre-rheumatoid arthritis (RA) diagnosis and post-RA diagnosis.
methodsUsing the Department of Defense Serum Repository we identified 214 RA cases and 210 matched controls. Up to 3 pre-RA diagnosis and 1 post-RA diagnosis serum samples per subject were tested for RF and for IgA, IgG, and IgM ACPAs. The timing and trajectories of elevations of autoantibodies were evaluated.
resultsAutoantibody levels were elevated in cases versus controls a mean of 17.9 years before RA diagnosis for IgG ACPA, 14.2 years for IgA-RF, 7.2 years for IgM-RF, 6.2 years for IgA ACPA, and 5.0 years for both IgM ACPA and IgG-RF (P < 0.01 for all comparisons). There were similar relationships for positive or negative autoantibody status, with cases first showing positivity for IgG ACPA 1.9 years pre-RA and for IgA-RF 1.7 years pre-RA, followed by the other isotypes. Only IgA ACPA positivity was significantly increased in post-RA diagnosis samples (19% 0-2 years pre-RA versus 39% >2 years post-RA diagnosis; P = 0.04). All autoantibody levels demonstrated an early initial elevation, a period of stability, then an increase immediately before RA diagnosis. A pre-RA endotype of early elevation of autoantibodies was associated with increased use of biologic therapy, and a higher prevalence of sicca symptoms and lung disease post-RA diagnosis.
conclusionDifferences in patterns of elevations of autoantibody isotypes have implications for understanding the pathophysiology of RA development. These include understanding what factors drive initial autoantibody elevations compared to what factors (including mucosal) drive later increases in autoantibody levels and a transition to clinically apparent RA, and how pre-RA endotypes may influence post-RA diagnosis phenotypes.
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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.