title: Autoantibodies against citrullinated histone H3 in rheumatoid arthritis and periodontitis patients.
abstract: OBJECTIVE
  To determine the presence of citrullinated histones in inflamed periodontal tissue and to determine the presence of anti-citrullinated histone autoantibodies in sera from patients with rheumatoid arthritis (RA) and periodontitis (PD) patients.
  
  
  METHODS
  The presence of citrullinated histone H3, PAD4 and CD68 was determined in 15 periodontal tissue biopsies from PD patients by immunohistochemistry. Sera from 36 healthy controls (HC), 113 PD patients and 84 patients with RA were assessed on presence of autoantibodies against citrullinated histones by Western blot and against citrullinated histone H3 by ELISA.
  
  
  RESULTS
  Citrullinated histone H3, PAD4 and CD68 were present in periodontal tissue from nine (60%), 14 (93%) and 13 (87%) PD patients, respectively. Anti-citrullinated histone H3 autoantibodies were found in 33 (39%) patients with RA compared to three (8%) HC and 11 (10%) PD patients. Anti-citrullinated histone H3 levels were higher in anti-cyclic citrullinated peptide (anti-CCP)-positive compared to anti-CCP-negative patients with RA (p = .0008) and correlated moderately with anti-CCP levels (ρ = .22). No associations were found between anti-citrullinated histone H3 levels and periodontal status or smoking behaviour of patients with RA.
  
  
  CONCLUSIONS
  PD patients are exposed to citrullinated histone H3 in inflamed periodontal tissue. Citrullinated histone H3 is targeted by autoantibodies present in RA sera. This supports a role for periodontitis in generation of antigens targeted by autoantibodies directed against citrullinated proteins.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Koen M J
authors.identifier: http://orcid.org/0000-0003-1297-4614
authors.initials: KMJ
authors.lastname: Janssen
authors.affiliation: Center for Dentistry and Oral Hygiene, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Menke J
authors.initials: MJ
authors.lastname: de Smit
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Coenraad
authors.initials: C
authors.lastname: Withaar
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brouwer
authors.affiliation: Center for Dentistry and Oral Hygiene, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.|Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Arie J
authors.initials: AJ
authors.lastname: van Winkelhoff
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Vissink
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Johanna
authors.initials: J
authors.lastname: Westra
mesh_terms: D000328:Adult; D000075422:Anti-Citrullinated Protein Antibodies / Q000097:blood / Q000276:immunology; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001706:Biopsy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006657:Histones / Q000097:blood / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D010518:Periodontitis / Q000276:immunology* / Q000473:pathology; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D012907:Smoking; D000097382:CD68 Molecule
chemical_list: D000075422:Anti-Citrullinated Protein Antibodies; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001323:Autoantibodies; D006657:Histones; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C000629235:PADI4 protein, human
keywords: ACPA; autoantibodies; citrullinated histone H3; periodontitis; rheumatoid arthritis