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Rheumatoid arthritis autoantibodies and their association with age and sex


1, 2, 3, 4, 5, 6, 7, 8, 9, 10

 

  1. Department of Immunology, Genetics and Pathology, University of Uppsala, Sweden.
  2. Department of Immunology, Genetics and Pathology, University of Uppsala, Sweden.
  3. Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
  4. Rheumatology Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institute, Stockholm, and Section of Rheumatology, Gastroenterology, Dermatology, Theme Inflammation, Karolinska University Hospital, Stockholm, Sweden.
  5. Center for Occupational and Environmental Medicine, Region Stockholm, Stockholm, and Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
  6. Department of Immunology, Genetics and Pathology, University of Uppsala, and Thermo Fisher Scientific, Uppsala, Sweden.
  7. Rheumatology Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
  8. Rheumatology Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden, and Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
  9. Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
  10. Department of Immunology, Genetics and Pathology, University of Uppsala, Sweden. johan.ronnelid@igp.uu.se

CER14341
Brief Papers

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PMID: 33822709 [PubMed]

Received: 18/12/2020
Accepted : 22/02/2021
In Press: 30/03/2021

Abstract

OBJECTIVES:
To examine the association between individual rheumatoid arthritis (RA) autoantibodies, sex and age at RA onset.
METHODS:
Anti-CCP2, IgA-, IgG- and IgM-RF were analysed centrally in baseline sera from 1600 RA patients diagnosed within one year of RA symptom onset. Cut-offs for RF isotypes were determined at the 98th percentile based on RA-free controls, close to the 98.4% anti-CCP2 specificity.
RESULTS:
Anti-CCP2 was found in 1020 patients (64%), IgA RF in 692 (43%), IgG RF in 529 (33%) and IgM RF in 916 (57%) of the patients. When assessed one by one, anti-CCP2 and IgM RF were both associated with lower age at RA diagnosis. When assessed in one joint model, the association to IgM RF weakened and a strong association between IgA RF and higher age at RA diagnosis appeared. IgA RF and IgG RF associated with male sex, and IgM RF with female sex, with no difference for anti-CCP2. When the model was adjusted for sex, the association between IgM RF and age disappeared, whereas the strong associations between IgA RF and high age and between anti-CCP2 and low age at diagnosis remained. Further adjustments for smoking, shared epitope and inclusion year did not change the outcome. Univariate analyses stratified on anti-CCP2 and IgA RF status confirmed the findings.
CONCLUSIONS:
Anti-CCP associate with low, and IgA RF with high age at RA onset. RFs and anti-CCP2 display opposing association with sex. These results underscore that studies on RA phenotypes in relation to autoantibodies should accommodate age and sex.

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