title: Periodontitis and Rheumatoid Arthritis: What Do We Know?
abstract: BACKGROUND
  Currently, in the field of rheumatology, there is much attention given towards the possible causality between periodontitis and rheumatoid arthritis (RA), specifically regarding the role of Porphyromonas gingivalis (Pg). This bacterium is unique, having a citrullinating enzyme. Antibodies against citrullinated proteins are rather specific for RA.
  
  
  METHODS
  Because causality is ultimately tested in longitudinal cohort studies which currently do not exist for periodontitis and RA, this commentary applied Bradford Hill criteria on the existing literature to assess causality as the most likely interpretation of this association.
  
  
  CONCLUSIONS
  From an epidemiologic point of view, patients with RA have a higher incidence of periodontal disease than individuals without RA. In addition, there is a dose-response pattern in the association between the severity of periodontitis and RA disease activity. There are indications that periodontitis precedes RA, but there is no evidence yet available to show that Pg plays a direct role in this temporal relationship. The role of the unique characteristic of citrullination by Pg remains unexplained. However, in animal models, citrullination by Pg plays a distinct role in the development and aggravation of experimental arthritis. Although the role of Pg in RA remains speculative, a causative role for periodontitis as a chronic inflammatory disease caused by infectious agents in RA seems biologically plausible.
authors.affiliation: Center for Dentistry and Oral Hygiene, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Menke J
authors.initials: MJ
authors.lastname: de Smit
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen and University Medical Center Groningen.
authors.forename: Johanna
authors.initials: J
authors.lastname: Westra
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen and University Medical Center Groningen.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brouwer
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Groningen and University Medical Center Groningen.
authors.forename: Koen M J
authors.initials: KM
authors.lastname: Janssen
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Groningen and University Medical Center Groningen.
authors.forename: Arjan
authors.initials: A
authors.lastname: Vissink
authors.affiliation: Center for Dentistry and Oral Hygiene, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.|Department of Medical Microbiology, University of Groningen and University Medical Center Groningen.
authors.forename: Arie Jan
authors.initials: AJ
authors.lastname: van Winkelhoff
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000382:microbiology*; D001323:Autoantibodies / Q000276:immunology; D002956:Citrulline / Q000276:immunology; D006801:Humans; D006867:Hydrolases / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000201:enzymology / Q000276:immunology*; D000076342:Protein-Arginine Deiminases; D053245:RANK Ligand / Q000276:immunology; D012217:Rheumatoid Factor / Q000276:immunology; D012307:Risk Factors; D013045:Species Specificity; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001323:Autoantibodies; D053245:RANK Ligand; D002956:Citrulline; D012217:Rheumatoid Factor; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases
keywords: Arthritis; Porphyromonas gingivalis; causality; periodontitis; rheumatoid