title: Anti-carbamylated Protein Antibody Levels Correlate with Anti-Sa (Citrullinated Vimentin) Antibody Levels in Rheumatoid Arthritis.
abstract: OBJECTIVE
  The presence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) indicates a breach in immune tolerance. Recent studies indicate that this breach extends to homocitrullination of lysines with the formation of anti-carbamylated protein (anti-CarP) antibodies. We analyzed the clinical and serologic relationships of anti-CarP in 2 RA cohorts.
  
  
  METHODS
  Circulating levels of immunoglobulin G anti-CarP antibodies were determined by ELISA in established (Dartmouth-Hitchcock Medical Center) and early (Sherbrooke University Hospital Center) cohorts and evaluated for anticyclic citrullinated peptide antibodies (anti-CCP), specific ACPA, and rheumatoid factor (RF) levels using the Student t test and correlation analysis.
  
  
  RESULTS
  We identified elevated anti-CarP antibodies titers in 47.0% of seropositive patients (Dartmouth, n = 164), with relationships to anti-CCP (p < 0.0001) and IgM-RF (p = 0.001). Similarly, 38.2% of seropositive patients from the Sherbrooke cohort (n = 171) had elevated anti-CarP antibodies; titers correlated to anti-CCP (p = 0.01) but not IgM-RF (p = 0.09). A strong correlation with anti-Sa was observed: 47.9% anti-Sa+ patients were anti-CarP antibodies+ versus only 25.4% anti-Sa- in the Sherbrooke cohort (p = 0.0002), and 62.6% anti-Sa+ patients versus 26.9% anti-Sa- were anti-CarP antibodies+ in Dartmouth (p < 0.0001). We found a more variable response for reactivity to citrullinated fibrinogen or to citrullinated peptides from fibrinogen and α enolase.
  
  
  CONCLUSIONS
  In 2 North American RA cohorts, we observed a high prevalence of anti-CarP antibody positivity. We also describe a surprising and unexpected association of anti-CarP with anti-Sa antibodies that could not be explained by cross-reactivity. Further, considerable heterogeneity exists between anti-CarP reactivity and other citrullinated peptide reactivity, raising the question of how the pathogenesis of antibody responses for carbamylated proteins and citrullinated proteins may be linked in vivo.
authors.affiliation: Geisel School of Medicine at Dartmouth College.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Challener
authors.affiliation: Geisel School of Medicine at Dartmouth College.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Jones
authors.affiliation: New University, School of Medicine, Departments of Medicine and Pathology.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Pelzek
authors.affiliation: Geisel School of Medicine at Dartmouth College.
authors.forename: B JoNell
authors.initials: BJ
authors.lastname: Hamilton
authors.affiliation: Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke.
authors.forename: Gilles
authors.initials: G
authors.lastname: Boire
authors.affiliation: Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke.
authors.forename: Artur José
authors.initials: AJ
authors.lastname: de Brum-Fernandes
authors.affiliation: Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke.
authors.forename: Ariel
authors.initials: A
authors.lastname: Masetto
authors.affiliation: Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Carrier
authors.affiliation: Research Institute of the McGill University Health Center.
authors.forename: Henri A
authors.initials: HA
authors.lastname: Ménard
authors.affiliation: New University, School of Medicine, Departments of Medicine and Pathology.
authors.forename: Gregg J
authors.initials: GJ
authors.lastname: Silverman
authors.affiliation: Geisel School of Medicine at Dartmouth College.
authors.forename: William F C
authors.initials: WFC
authors.lastname: Rigby
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D014746:Vimentin / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide
keywords: AUTOANTIBODIES; CYCLIC CITRULLINATED PEPTIDE; RHEUMATOID ARTHRITIS; VIMENTIN