ArticleArthritis and rheumatism2013
Relatives without rheumatoid arthritis show reactivity to anti-citrullinated protein/peptide antibodies that are associated with arthritis-related traits: studies of the etiology of rheumatoid arthritis.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 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
- Secretory antibodies to citrullinated peptides in plasma and saliva from rheumatoid arthritis patients and their unaffected first-degree relatives.Clinical and experimental immunology · 2020Trial
- Biological mechanisms of pulmonary inflammation and its association with seropositive rheumatoid arthritis.Frontiers in immunology · 2025Review
- Distinct mucosal endotypes as initiators and drivers of rheumatoid arthritis.Nature reviews. Rheumatology · 2024Review
- Anti-citrullinated protein antibody profiles predict changes in disease activity in patients with rheumatoid arthritis initiating biologics.Rheumatology (Oxford, England) · 2024Article
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- Article
- Family History of Rheumatic, Autoimmune, and Nonautoimmune Diseases and Risk of Rheumatoid Arthritis.Arthritis care & research · 2021Article
- Impact of Cyclic Citrullinated Peptide Antibody Level on Progression to Rheumatoid Arthritis in Clinically Tested Cyclic Citrullinated Peptide Antibody-Positive Patients Without Rheumatoid Arthritis.Arthritis care & research · 2019Article
- Association between seropositivity and discontinuation of tumor necrosis factor inhibitors due to ineffectiveness in rheumatoid arthritis.Clinical rheumatology · 2019Observational
- Potential of Lifestyle Changes for Reducing the Risk of Developing Rheumatoid Arthritis: Is an Ounce of Prevention Worth a Pound of Cure?Clinical therapeutics · 2019Review
- Latent autoimmunity across disease-specific boundaries in at-risk first-degree relatives of SLE and RA patients.EBioMedicine · 2019Article
- Autoimmunity, inflammation, and dysbiosis mutually govern the transition from the preclinical to the clinical stage of rheumatoid arthritis.Immunologic research · 2018Review
- Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction.Nature reviews. Rheumatology · 2018Review
- Differing specificities and isotypes of anti-citrullinated peptide/protein antibodies in palindromic rheumatism and rheumatoid arthritis.Arthritis research & therapy · 2017Article
- Association of Antibodies to Citrullinated Protein Antigens with Blood Pressure in First-Degree Relatives of Rheumatoid Arthritis Patients: The Studies of the Etiology of Rheumatoid Arthritis.American journal of nephrology · 2017Article
- Elevated IgA Plasmablast Levels in Subjects at Risk of Developing Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- T cell subsets: an immunological biomarker to predict progression to clinical arthritis in ACPA-positive individuals.Annals of the rheumatic diseases · 2016Observational
- Editorial: IgA Responses and Future Development of Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- The genetics of rheumatoid arthritis: risk and protection in different stages of the evolution of RA.Rheumatology (Oxford, England) · 2016Review
Corrections and comments
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Authors and funding
15 authors at 10 institutions in 1 country.
Funding
Abstract
objectiveTo examine reactivity to anti-citrullinated protein/peptide antibodies (ACPAs) and determine associations between ACPAs and other rheumatoid arthritis (RA)-related autoantibodies and clinically assessed swollen or tender joints in unaffected first-degree relatives of RA patients.
methodsSerum samples were obtained from first-degree relatives without RA according to the 1987 American College of Rheumatology (ACR) and the 2010 ACR/European League Against Rheumatism classification criteria. A bead-based assay was used to measure 16 separate ACPAs in sera from 111 antibody-positive first-degree relatives who were positive on at least 1 visit for any of 5 RA-related autoantibodies (rheumatoid factor [RF], anti-cyclic citrullinated peptide 2 [anti-CCP-2], and RF isotypes), and sera from 99 antibody-negative first-degree relatives who were never autoantibody positive. Cutoffs for positivity for each ACPA were determined using receiver operating characteristic curves derived from data on 200 RA patients and 98 blood donor controls, in which positivity for ≥9 ACPAs had 92% specificity and 62% sensitivity for RA. In first-degree relatives, ACPA reactivity was assessed, and associations between ACPAs (number positive, and positivity for ≥9 ACPAs) and RA-related characteristics were examined.
resultsFifty-seven percent of anti-CCP-2-positive first-degree relatives and 8% of anti-CCP-2- negative first-degree relatives were positive for ≥9 ACPAs. After adjusting for age, sex, ethnicity, and pack-years of smoking, an increasing number of ACPAs was directly associated with the presence of ≥1 tender joint on examination (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 1.04-1.34), with the greatest risk of having ≥1 tender joint seen in first-degree relatives positive for ≥9 ACPAs (OR 5.00, 95% CI 1.37-18.18).
conclusionRA-free first-degree relatives (even those negative for RF and anti-CCP-2) demonstrate reactivity to multiple ACPAs, and the presence of an increasing number of ACPAs may be associated with signs of joint inflammation. Prospective evaluation of the relationship between these findings and the progression of classifiable RA is warranted.
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