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Anti-CarP antibodies in two large cohorts of patients with rheumatoid arthritis and their relationship to genetic risk factors, cigarette smoking and other autoantibodies
  1. Xia Jiang1,
  2. Leendert A Trouw2,
  3. Tineke J van Wesemael2,
  4. Jing Shi2,
  5. Camilla Bengtsson1,
  6. Henrik Källberg1,
  7. Vivi Malmström3,
  8. Lena Israelsson3,
  9. Hulda Hreggvidsdottir3,
  10. Willem Verduijn4,
  11. Lars Klareskog3,
  12. Lars Alfredsson1,5,
  13. Tom W J Huizinga2,
  14. Rene E M Toes2,
  15. Karin Lundberg3,
  16. Diane van der Woude2
  1. 1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  2. 2Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
  4. 4Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
  5. 5Center for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
  1. Correspondence to Dr Diane van der Woude, Leiden University Medical Center, Department of Rheumatology, C1-40, PO Box 9600, 2300 RC Leiden, The Netherlands; dvanderwoude{at}lumc.nl

Abstract

Introduction In rheumatoid arthritis (RA), several genetic risk factors and smoking are strongly associated with the presence of anticitrullinated protein antibodies (ACPA), while much less is known about risk factors for ACPA-negative RA. Antibodies against carbamylated proteins (anti-CarP) have been described in both ACPA-positive and ACPA-negative RA patients. In this study, we have analysed the relationships among anti-CarP antibodies, ACPA, genetic risk factors (HLA-DRB1 alleles and PTPN22) and smoking in RA.

Methods Presence of antibodies to carbamylated fetal calf serum (CarP-FCS) and fibrinogen (CarP-Fib) was determined by inhouse ELISAs among RA cases in the Leiden Early Arthritis Clinic (n=846) and in the Swedish Epidemiological Investigation of Rheumatoid Arthritis (n=1985) cohorts. ORs for associations with different HLA-DRB1 alleles, PTPN22 genotypes and smoking were calculated separately for each cohort as well as in meta-analysis in RA subsets defined by the presence/absence of anti-CarP and anticyclic citrullinated peptide (anti-CCP) antibodies.

Results In both cohorts, anti-CarP antibody positivity was mainly detected in the anti-CCP-positive population (49%–73%), but also in the anti-CCP-negative population (8%–14%). No associations between anti-CarP antibodies and HLA-DRB1 shared epitope alleles could be identified, while there were data to support an association between anti-CarP-FCS and HLA-DRB1*03. Further analyses did not reveal any specific associations of anti-CarP antibodies with other HLA-DRB1 alleles, PTPN22 genotypes or smoking.

Conclusions Anti-CarP antibodies were present in both ACPA-positive and ACPA-negative RA. There were no significant associations among anti-CarP antibodies and HLA-DRB1 alleles, PTPN22 or smoking. These data suggest that different biological mechanisms may underlie anti-CarP versus anti-CCP antibody formation.

  • Autoantibodies
  • Rheumatoid Arthritis
  • Epidemiology
  • Gene Polymorphism

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