title: Antibodies to porphyromonas gingivalis are associated with anticitrullinated protein antibodies in patients with rheumatoid arthritis and their relatives.
abstract: OBJECTIVE
  Anticitrullinated protein antibodies (ACPA) are relatively specific for rheumatoid arthritis (RA), and predate disease. The oral pathogen Porphyromonas gingivalis may play a role in breaking immune tolerance to citrullinated antigens. We studied a cohort of patients with RA and their relatives looking for associations between anti-P. gingivalis antibodies and ACPA.
  
  
  METHODS
  Patients with RA (n = 82) and their relatives (n = 205) from a North American Native (NAN) population were studied, along with 47 NAN and 60 non-NAN controls. IgM and IgA rheumatoid factor (RF) were tested by nephelometry and ELISA. Second-generation anticyclic citrullinated peptide (anti-CCP2) isotypes and IgG anti-P. gingivalis lipopolysaccharides were tested by ELISA. HLA-DRB1 typing was performed by sequencing. Oral hygiene and smoking habits were assessed by questionnaires.
  
  
  RESULTS
  Autoantibody frequency in patients with RA and relatives: ACPA 91% vs 19%, respectively; IgM RF 82% vs 17%; IgA RF 48% vs 22%. Anti-P. gingivalis levels were higher in patients with RA compared to relatives and controls (p = 0.005) and higher in ACPA-positive patients with RA than in ACPA-negative patients with RA (p = 0.04) and relatives (p < 0.001), but comparable in RF-positive and RF-negative patients and relatives. Poor oral hygiene and smoking were prevalent, but with no clear association with autoantibodies. Relatives with 2 shared-epitope alleles were more likely to be ACPA-positive (OR 2.5, p = 0.02).
  
  
  CONCLUSIONS
  In a genetically predisposed population of NAN patients with RA and their relatives, anti-P. gingivalis antibodies were associated with ACPA. These findings suggest that immune responses to P. gingivalis may be involved in breaking immune tolerance to citrullinated antigens.
authors.affiliation: University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Hitchon
authors.forename: Fatiha
authors.initials: F
authors.lastname: Chandad
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Ferucci
authors.forename: Annemiek
authors.initials: A
authors.lastname: Willemze
authors.forename: Andreea
authors.initials: A
authors.lastname: Ioan-Facsinay
authors.forename: Diane
authors.initials: D
authors.lastname: van der Woude
authors.forename: Janet
authors.initials: J
authors.lastname: Markland
authors.forename: David
authors.initials: D
authors.lastname: Robinson
authors.forename: Brenda
authors.initials: B
authors.lastname: Elias
authors.forename: Marianna
authors.initials: M
authors.lastname: Newkirk
authors.forename: Rene M
authors.initials: RM
authors.lastname: Toes
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Hani S
authors.initials: HS
authors.lastname: El-Gabalawy
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D002170:Canada / Q000453:epidemiology; D015331:Cohort Studies; D003731:Dental Caries / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007198:Indians, North American; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D012217:Rheumatoid Factor / Q000097:blood / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor