{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T03:45:16Z","timestamp":1766720716175,"version":"3.44.0"},"reference-count":20,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"unspecified","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007949","name":"Reumatikerf\u00f6rbundet","doi-asserted-by":"publisher","award":["R-980953"],"award-info":[{"award-number":["R-980953"]}],"id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science Center","award":["UMO-2018\/30\/A\/NZ5\/00650"],"award-info":[{"award-number":["UMO-2018\/30\/A\/NZ5\/00650"]}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["772209 PREVENT RA"],"award-info":[{"award-number":["772209 PREVENT RA"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2017-00359"],"award-info":[{"award-number":["2017-00359"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007857","name":"Stiftelsen Konung Gustaf V:s 80-\u00e5rsfond","doi-asserted-by":"publisher","award":["FAI-2021-0771","FAI-2022-0856"],"award-info":[{"award-number":["FAI-2021-0771","FAI-2022-0856"]}],"id":[{"id":"10.13039\/501100007857","id-type":"DOI","asserted-by":"publisher"}]},{"name":"US NIH\/NIDCR","award":["DE 022597"],"award-info":[{"award-number":["DE 022597"]}]},{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","award":["777357 RTCure"],"award-info":[{"award-number":["777357 RTCure"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,1,15]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The antibody response against <jats:italic>Porphyromonas gingivalis<\/jats:italic> (<jats:italic>Pg<\/jats:italic>) is elevated in rheumatoid arthritis (RA), especially in patients with anti-citrullinated protein antibodies (ACPA). Here, we investigated whether antibodies against the <jats:italic>Pg<\/jats:italic> virulence factor arginine gingipain (Rgp) are associated with the RA-risk phase and development of arthritis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>At-risk individuals were included in a prospective study (Risk-RA) based on a positive anti-cyclic citrullinated peptide 2 (CCP2) antibody test, and having musculoskeletal complaints but no signs of arthritis. Study participants were followed for \u22653 years (arthritis-free, n=165) or until arthritis onset (progressors, n=95). Anti-Rgp IgG was measured in Risk-RA (260 baseline and 247 follow-up samples) and healthy controls (n=126); anti-CCP2 IgG was measured in Risk-RA (254 baseline samples). Data were analysed in GraphPad Prism and R using log-transformed antibody levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>53% of Risk-RA and 26% of controls, p=0.003, were anti-Rgp IgG positive at baseline, with higher levels in Risk-RA compared with controls, p&lt;0.0001. No changes in anti-Rgp IgG levels were observed during follow-up. The anti-Rgp IgG response at baseline did not associate with the development of arthritis; Cox-regression showed an HR of 0.95 (CI 0.80 to 1.13, p=0.6) for anti-Rgp IgG levels, and 0.82 (CI 0.55 to 1.23, p=0.3) for anti-Rgp IgG positivity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Antibodies against the oral bacterium <jats:italic>Pg<\/jats:italic> are elevated during the RA-risk phase, both in individuals progressing to arthritis and in individuals remaining arthritis-free. Hence, <jats:italic>Pg<\/jats:italic> infection can be linked to the presence of RA-specific autoimmunity, ACPA, and musculoskeletal symptoms, but not to further development of arthritis in this at-risk population.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2024-005111","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T12:05:38Z","timestamp":1738325138000},"page":"e005111","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["<i>Porphyromonas gingivalis<\/i> associates with the presence of anti-citrullinated protein antibodies, but not with the onset of arthritis: studies in an at-risk population"],"prefix":"10.1136","volume":"11","author":[{"given":"Charlotte","family":"De Vries","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0009-7345","authenticated-orcid":false,"given":"Alexandra","family":"C\u00eerciumaru","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden"},{"name":"Center for Rheumatology, Academic Specialist Center, Stockholm Health Services, Region Stockholm, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Mathsson-Alm","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden"},{"name":"Thermo Fisher Scientific, ImmunoDiagnostics Division, Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3380-5342","authenticated-orcid":false,"given":"Helga","family":"Westerlind","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Dehara","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3988-1629","authenticated-orcid":false,"given":"Yogan","family":"Kisten","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Potempa","sequence":"additional","affiliation":[{"name":"Department of Oral Immunology & Infectious Diseases, School of Dentistry, University of Louisville, Louisville, Kentucky, USA"},{"name":"Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Potempa","sequence":"additional","affiliation":[{"name":"Department of Oral Immunology & Infectious Diseases, School of Dentistry, University of Louisville, Louisville, Kentucky, USA"},{"name":"Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aase","family":"Hensvold","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden"},{"name":"Center for Rheumatology, Academic Specialist Center, Stockholm Health Services, Region Stockholm, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7625-964X","authenticated-orcid":false,"given":"Karin","family":"Lundberg","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"2025090312441176000_11.1.e005111.1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2016.00080","article-title":"Hand to Mouth: A Systematic Review and Meta-Analysis of the Association between Rheumatoid Arthritis and Periodontitis","volume":"7","author":"Fuggle","year":"2016","journal-title":"Front Immunol"},{"key":"2025090312441176000_11.1.e005111.2","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abq8476","article-title":"Oral mucosal breaks trigger anti-citrullinated bacterial and human protein antibody responses in rheumatoid arthritis","volume":"15","author":"Brewer","year":"2023","journal-title":"Sci Transl Med"},{"key":"2025090312441176000_11.1.e005111.3","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-004-6641-z"},{"key":"2025090312441176000_11.1.e005111.4","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.7.3248-3256.1999"},{"key":"2025090312441176000_11.1.e005111.5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007773","article-title":"Triggering NETosis via protease-activated receptor (PAR)-2 signaling as a mechanism of hijacking neutrophils function for pathogen benefits","volume":"15","author":"Bryzek","year":"2019","journal-title":"PLoS Pathog"},{"key":"2025090312441176000_11.1.e005111.6","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1002\/art.39491","article-title":"Antibodies to Porphyromonas gingivalis Indicate Interaction Between Oral Infection, Smoking, and Risk Genes in Rheumatoid Arthritis Etiology","volume":"68","author":"Kharlamova","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"2025090312441176000_11.1.e005111.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-016-1938-5"},{"key":"2025090312441176000_11.1.e005111.8","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2019.5394","article-title":"Prevalence of Periodontal Disease and Periodontopathic Bacteria in Anti-Cyclic Citrullinated Protein Antibody-Positive At-Risk Adults Without Arthritis","volume":"2","author":"Mankia","year":"2019","journal-title":"JAMA Netw Open"},{"key":"2025090312441176000_11.1.e005111.9","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-016-1100-4","article-title":"Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis","volume":"18","author":"Johansson","year":"2016","journal-title":"Arthritis Res Ther"},{"key":"2025090312441176000_11.1.e005111.10","doi-asserted-by":"crossref","DOI":"10.1186\/s12891-015-0792-y","article-title":"Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study","volume":"16","author":"Fisher","year":"2015","journal-title":"BMC Musculoskelet Disord"},{"key":"2025090312441176000_11.1.e005111.11","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1093\/rheumatology\/keae146","article-title":"Identification of early risk factors for anti-citrullinated-protein-antibody positive rheumatoid arthritis-a prospective cohort study","volume":"63","author":"C\u00eerciumaru","year":"2024","journal-title":"Rheumatology (Oxford)"},{"key":"2025090312441176000_11.1.e005111.12","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204594"},{"key":"2025090312441176000_11.1.e005111.13","doi-asserted-by":"crossref","first-page":"152176","DOI":"10.1016\/j.semarthrit.2023.152176","article-title":"Serum antibodies to periodontal pathogens prior to rheumatoid arthritis diagnosis: A case-control study","volume":"59","author":"Lee","year":"2023","journal-title":"Semin Arthritis Rheum"},{"key":"2025090312441176000_11.1.e005111.14","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA119.001700"},{"key":"2025090312441176000_11.1.e005111.15","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.01017","article-title":"Identification and Modification of Porphyromonas gingivalis Cysteine Protease, Gingipain, Ideal for Screening Periodontitis","volume":"11","author":"Hirai","year":"2020","journal-title":"Front Immunol"},{"key":"2025090312441176000_11.1.e005111.16","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11041008","article-title":"Antibodies to Porphyromonas gingivalis Are Increased in Patients with Severe Periodontitis, and Associate with Presence of Specific Autoantibodies and Myocardial Infarction","volume":"11","author":"de Vries","year":"2022","journal-title":"J Clin Med"},{"key":"2025090312441176000_11.1.e005111.17","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/jre.12486","article-title":"Gingival tissue, an extrasynovial source of malondialdehyde-acetaldehyde adducts, citrullinated and carbamylated proteins","volume":"53","author":"Bright","year":"2018","journal-title":"J Periodontal Res"},{"key":"2025090312441176000_11.1.e005111.18","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.804822","article-title":"Antibodies to a Citrullinated Porphyromonas gingivalis Epitope Are Increased in Early Rheumatoid Arthritis, and Can Be Produced by Gingival Tissue B Cells: Implications for a Bacterial Origin in RA Etiology","volume":"13","author":"Sherina","year":"2022","journal-title":"Front Immunol"},{"key":"2025090312441176000_11.1.e005111.19","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12002"},{"key":"2025090312441176000_11.1.e005111.20","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1002\/art.40880","article-title":"A Prospective Study of the Development of Inflammatory Arthritis in the Family Members of Indigenous North American People With Rheumatoid Arthritis","volume":"71","author":"Tanner","year":"2019","journal-title":"Arthritis Rheumatol"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2024-005111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T19:44:18Z","timestamp":1756928658000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2024-005111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,31]]},"published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1136\/rmdopen-2024-005111"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2024-005111","relation":{},"ISSN":["2056-5933"],"issn-type":[{"type":"electronic","value":"2056-5933"}],"subject":[],"published":{"date-parts":[[2025,1]]}}}