title: Prevalence of anti-peptidylarginine deiminase type 4 antibodies in rheumatoid arthritis and unaffected first-degree relatives in indigenous North American Populations.
abstract: OBJECTIVE
  To determine whether anti-peptidylarginine deiminase type 4 (PAD4) antibodies were present in first-degree relatives (FDR) of patients with rheumatoid arthritis (RA) in 2 indigenous North American populations with high prevalence of RA.
  
  
  METHODS
  Participants were recruited from 2 indigenous populations in Canada and the United States, including patients with RA (probands), their unaffected FDR, and healthy unrelated controls. Sera were tested for the presence of anti-PAD4 antibodies, anticyclic citrullinated peptide (anti-CCP) antibodies, and rheumatoid factor (RF). HLA-DRB1 subtyping was performed and participants were classified according to number of shared-epitope alleles present.
  
  
  RESULTS
  Antibodies to PAD4 were detected in 24 of 82 (29.3%) probands; 2 of 147 (1.4%) relatives; and no controls (p < 0.0001). Anti-CCP was present in 39/144 (27.1%) of the relatives, and there was no overlap between positivity for anti-CCP and PAD4 in the relatives. In RA patients, anti-PAD4 antibodies were associated with disease duration (p = 0.0082) and anti-CCP antibodies (p = 0.008), but not smoking or shared-epitope alleles.
  
  
  CONCLUSIONS
  Despite a significant prevalence of anti-CCP in FDR, anti-PAD4 antibodies were almost exclusively found in established RA. The prevalence of anti-PAD4 antibodies in RA is similar to the prevalence described in other populations and these autoantibodies are associated with disease duration and anti-CCP in RA.
authors.affiliation: Division of Community Health Services, Alaska Native Tribal Health Consortium, Anchorage, Alaska, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Ferucci
authors.forename: Erika
authors.initials: E
authors.lastname: Darrah
authors.forename: Irene
authors.initials: I
authors.lastname: Smolik
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Choromanski
authors.forename: David B
authors.initials: DB
authors.lastname: Robinson
authors.forename: Marianna M
authors.initials: MM
authors.lastname: Newkirk
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
authors.forename: Antony
authors.initials: A
authors.lastname: Rosen
authors.forename: Hani S
authors.initials: HS
authors.lastname: El-Gabalawy
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000235:genetics / Q000276:immunology*; D002170:Canada; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006867:Hydrolases / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D014481:United States
chemical_list: D001323:Autoantibodies; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
keywords: ARTHRITIS; AUTOANTIBODIES; PEPTIDYLARGININE DEIMINASE; RHEUMATOID
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