title: Serum autoantibodies that bind citrullinated fibrinogen are frequently found in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Autoantibodies that bind citrullinated antigens are a sensitive and specific marker for rheumatoid arthritis (RA). While synthetic cyclic citrullinated peptides (CCP) are typically used to identify these antibodies, little is known about antibody reactivity to the predominant citrullinated protein found in the inflamed synovium, citrullinated fibrinogen (CitFib). We assessed the prevalence of anti-CitFib antibodies in patients with various rheumatic diseases.
  
  
  METHODS
  In total, 65 patients with established RA and 63 patients with other rheumatic diseases were tested for serum IgM rheumatoid factor (RF), IgG anti-CCP2, and IgG anti-CitFib antibodies. This cohort was used to determine optimal positive cutoff values for antibody reactivity to CitFib through receiver operating characteristic curve analysis. The specificity of these assays was confirmed with sera from 49 patients with psoriatic arthritis.
  
  
  RESULTS
  Antibodies to both citrullinated antigens were identified in the majority of RA patients tested. The overall sensitivity and specificity of the assays were: CCP 82%, 96%, CitFib 75%, 98%, and IgM RF 80%, 64%, respectively. All but one patient that was positive for CitFib was also positive for CCP2, and close to half the RF-negative RA patients were positive for CitFib and CCP2.
  
  
  CONCLUSIONS
  These results suggest that autoimmunity to CitFib is common in patients with RA and may play a role in disease pathogenesis.
authors.affiliation: Department of Medicine, Division of Rheumatology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Hill
authors.forename: Jamal
authors.initials: J
authors.lastname: Al-Bishri
authors.forename: Dafna D
authors.initials: DD
authors.lastname: Gladman
authors.forename: Ewa
authors.initials: E
authors.lastname: Cairns
authors.forename: David A
authors.initials: DA
authors.lastname: Bell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D002956:Citrulline; D005260:Female; D005340:Fibrinogen / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood* / Q000276:immunology; D011237:Predictive Value of Tests; D012372:ROC Curve; D012217:Rheumatoid Factor / Q000097:blood*; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002956:Citrulline; D005340:Fibrinogen; D012217:Rheumatoid Factor