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Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present
  1. V F A M Derksen1,
  2. S Ajeganova1,2,
  3. L A Trouw1,
  4. A H M van der Helm-van Mil1,
  5. I Hafström2,
  6. T W J Huizinga1,
  7. R E M Toes1,
  8. B Svensson3,
  9. D van der Woude1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
  3. 3Section of Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden
  1. Correspondence to Dr Diane van der Woude, Department of Rheumatology, Leiden University Medical Center, C1-R-041, Albinusdreef 2, PO Box 9600, Leiden 2300 RC, The Netherlands; dvanderwoude{at}


Objectives In rheumatoid arthritis (RA), seropositive and seronegative disease may be two entities with different underlying pathophysiological mechanisms, long-term outcomes and disease presentations. However, the effect of the conjoint presence of multiple autoantibodies, as proxy for a more pronounced humoral autoimmune response, on clinical phenotype remains unclear. Therefore, this study investigates the association between the number of autoantibodies and initial clinical presentation in two independent cohorts of patients with early RA.

Methods Autoantibody status (rheumatoid factor, anticitrullinated protein antibodies and anticarbamylated protein antibodies) was determined at baseline in the Leiden Early Arthritis Cohort (n=828) and the Swedish BARFOT (Better Anti-Rheumatic Farmaco-Therapy, n=802) study. The association between the number of autoantibodies and baseline clinical characteristics was investigated using univariable and multivariable ordinal regression.

Results In both cohorts, the following independent associations were found in multivariable analysis: patients with a higher number of RA-associated antibodies were younger, more often smokers, had a longer symptom duration and a higher erythrocyte sedimentation rate at presentation compared with patients with few autoantibodies.

Conclusions The number of autoantibodies, reflecting the breadth of the humoral autoimmune response, is associated with the clinical presentation of RA. Predisease pathophysiology is thus reflected by the initial clinical phenotype.

  • Rheumatoid Arthritis
  • Autoantibodies
  • Autoimmunity

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  • Handling editor Tore K Kvien

  • Contributors All authors were involved in study design, data collection and interpretation and approved the final version of the manuscript. VFAMD and DvdW performed the statistical analyses and wrote the manuscript.

  • Funding This study was supported by the European Union Seventh Framework Programme integrated project Euro-TEAM.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethics Committee of the Leiden University Medical Center; regional ethics committee in Stockholm, Sweden.

  • Provenance and peer review Not commissioned; externally peer reviewed.