title: Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: V F A M
authors.initials: VF
authors.lastname: Derksen
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.|Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Ajeganova
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: L A
authors.initials: LA
authors.lastname: Trouw
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Hafström
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: R E M
authors.initials: RE
authors.lastname: Toes
authors.affiliation: Section of Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Svensson
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: van der Woude
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001799:Blood Sedimentation; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D010641:Phenotype; D012217:Rheumatoid Factor / Q000276:immunology*; D012907:Smoking
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; D012217:Rheumatoid Factor
keywords: Autoantibodies; Autoimmunity; Rheumatoid Arthritis