Nastya Kharlamova1, Xia Jiang1, Natalia Sherina1, Barbara Potempa2, Lena Israelsson1, Anne-Marie Quirke3, Kaja Eriksson1, Tülay Yucel-Lindberg1, Patrick J Venables3, Jan Potempa4, Lars Alfredsson5, Karin Lundberg1. 1. Karolinska Institutet, Stockholm, Sweden. 2. University of Louisville School of Dentistry, Louisville, Kentucky. 3. Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, and University of Oxford, Oxford, UK. 4. University of Louisville School of Dentistry, Louisville, Kentucky, and Jagiellonian University, Krakow, Poland. 5. Karolinska Institutet and Centre for Occupational and Environmental Medicine at Stockholm County Council, Stockholm, Sweden.
Abstract
OBJECTIVE: To investigate the role of the periodontal pathogen Porphyromonas gingivalis in the etiology of rheumatoid arthritis (RA) by analyzing the antibody response to the P gingivalis virulence factor arginine gingipain type B (RgpB) in relation to anti-citrullinated protein antibodies (ACPAs), smoking, and HLA-DRB1 shared epitope (SE) alleles in patients with periodontitis, patients with RA, and controls. METHODS: Anti-RgpB IgG was measured by enzyme-linked immunosorbent assay in 65 periodontitis patients and 59 controls without periodontitis, and in 1,974 RA patients and 377 controls without RA from the Swedish population-based case-control Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study. Autoantibody status, smoking habits, and genetic data were retrieved from the EIRA database. Differences in antibody levels were examined using the Mann-Whitney U test. Unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs) for the association of anti-RgpB IgG with different subsets of RA patients. RESULTS: Anti-RgpB antibody levels were significantly elevated in periodontitis patients compared to controls without periodontitis, in RA patients compared to controls without RA, and in ACPA-positive RA patients compared to ACPA-negative RA patients. There was a significant association between anti-RgpB IgG and RA (OR 2.96 [95% CI 2.00, 4.37]), which was even stronger than the association between smoking and RA (OR 1.37 [95% CI 1.07, 1.74]), and in ACPA-positive RA there were interactions between anti-RgpB antibodies and both smoking and the HLA-DRB1 SE. CONCLUSION: Our study suggests that the previously reported link between periodontitis and RA could be accounted for by P gingivalis infection, and we conclude that P gingivalis is a credible candidate for triggering and/or driving autoimmunity and autoimmune disease in a subset of RA patients.
OBJECTIVE: To investigate the role of the periodontal pathogen Porphyromonas gingivalis in the etiology of rheumatoid arthritis (RA) by analyzing the antibody response to the P gingivalis virulence factor arginine gingipain type B (RgpB) in relation to anti-citrullinated protein antibodies (ACPAs), smoking, and HLA-DRB1 shared epitope (SE) alleles in patients with periodontitis, patients with RA, and controls. METHODS: Anti-RgpB IgG was measured by enzyme-linked immunosorbent assay in 65 periodontitispatients and 59 controls without periodontitis, and in 1,974 RApatients and 377 controls without RA from the Swedish population-based case-control Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study. Autoantibody status, smoking habits, and genetic data were retrieved from the EIRA database. Differences in antibody levels were examined using the Mann-Whitney U test. Unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs) for the association of anti-RgpB IgG with different subsets of RApatients. RESULTS: Anti-RgpB antibody levels were significantly elevated in periodontitispatients compared to controls without periodontitis, in RApatients compared to controls without RA, and in ACPA-positive RApatients compared to ACPA-negative RApatients. There was a significant association between anti-RgpB IgG and RA (OR 2.96 [95% CI 2.00, 4.37]), which was even stronger than the association between smoking and RA (OR 1.37 [95% CI 1.07, 1.74]), and in ACPA-positive RA there were interactions between anti-RgpB antibodies and both smoking and the HLA-DRB1 SE. CONCLUSION: Our study suggests that the previously reported link between periodontitis and RA could be accounted for by P gingivalis infection, and we conclude that P gingivalis is a credible candidate for triggering and/or driving autoimmunity and autoimmune disease in a subset of RApatients.
Authors: Solbritt Rantapää-Dahlqvist; Ben A W de Jong; Ewa Berglin; Göran Hallmans; Göran Wadell; Hans Stenlund; Ulf Sundin; Walther J van Venrooij Journal: Arthritis Rheum Date: 2003-10
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