Koen M J Janssen1, Menke J de Smit2, Coenraad Withaar3, Elisabeth Brouwer3, Arie J van Winkelhoff2,4, Arjan Vissink1, Johanna Westra3. 1. Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 2. Center for Dentistry and Oral Hygiene, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 3. Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 4. Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Abstract
AIM: 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. CONCLUSION: 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.
AIM: 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 PDpatients by immunohistochemistry. Sera from 36 healthy controls (HC), 113 PDpatients 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%) PDpatients, respectively. Anti-citrullinated histone H3 autoantibodies were found in 33 (39%) patients with RA compared to three (8%) HC and 11 (10%) PDpatients. 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. CONCLUSION:PDpatients 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: Tim Stobernack; Marines du Teil Espina; Lianne M Mulder; Laura M Palma Medina; Dillon R Piebenga; Giorgio Gabarrini; Xin Zhao; Koen M J Janssen; Jarnick Hulzebos; Elisabeth Brouwer; Thomas Sura; Dörte Becher; Arie Jan van Winkelhoff; Friedrich Götz; Andreas Otto; Johanna Westra; Jan Maarten van Dijl Journal: mBio Date: 2018-10-30 Impact factor: 7.867