Serum antibodies to periodontal pathogens prior to rheumatoid arthritis diagnosis: A case-control study
1) To quantify the association between anti-Porphyromonas gingivalis serum antibody concentrations and the risk of developing rheumatoid arthritis (RA), and 2) to quantify the associations among RA cases between anti-P. gingivalis serum antibody concentrations and RA-specific autoantibodies. Additio...
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Published in | Seminars in arthritis and rheumatism Vol. 59; p. 152176 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Elsevier Inc
01.04.2023
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Abstract | 1) To quantify the association between anti-Porphyromonas gingivalis serum antibody concentrations and the risk of developing rheumatoid arthritis (RA), and 2) to quantify the associations among RA cases between anti-P. gingivalis serum antibody concentrations and RA-specific autoantibodies. Additional anti-bacterial antibodies evaluated included anti-Fusobacterium nucleatum and anti-Prevotella intermedia.
Serum samples were acquired pre- and post- RA diagnosis from the U.S. Department of Defense Serum Repository (n = 214 cases, 210 matched controls). Using separate mixed-models, the timing of elevations of anti-P. gingivalis, anti-P. intermedia, and anti-F. nucleatum antibody concentrations relative to RA diagnosis were compared in RA cases versus controls. Associations were determined between serum anti-CCP2, ACPA fine specificities (vimentin, histone, and alpha-enolase), and IgA, IgG, and IgM RF in pre-RA diagnosis samples and anti-bacterial antibodies using mixed-effects linear regression models.
No compelling evidence of case-control divergence in serum anti-P. gingivalis, anti-F. nucleatum, and anti-P. intermedia was observed. Among RA cases, including all pre-diagnosis serum samples, anti-P. intermedia was significantly positively associated with anti-CCP2, ACPA fine specificities targeting vimentin, histone, alpha-enolase, and IgA RF (p<0.001), IgG RF (p = 0.049), and IgM RF (p = 0.004), while anti-P. gingivalis and anti-F. nucleatum were not.
No longitudinal elevations of anti-bacterial serum antibody concentrations were observed in RA patients prior to RA diagnosis compared to controls. However, anti-P. intermedia displayed significant associations with RA autoantibody concentrations prior to RA diagnosis, suggesting a potential role of this organism in progression towards clinically-detectable RA.
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AbstractList | OBJECTIVES1) To quantify the association between anti-Porphyromonas gingivalis serum antibody concentrations and the risk of developing rheumatoid arthritis (RA), and 2) to quantify the associations among RA cases between anti-P. gingivalis serum antibody concentrations and RA-specific autoantibodies. Additional anti-bacterial antibodies evaluated included anti-Fusobacterium nucleatum and anti-Prevotella intermedia.METHODSSerum samples were acquired pre- and post- RA diagnosis from the U.S. Department of Defense Serum Repository (n = 214 cases, 210 matched controls). Using separate mixed-models, the timing of elevations of anti-P. gingivalis, anti-P. intermedia, and anti-F. nucleatum antibody concentrations relative to RA diagnosis were compared in RA cases versus controls. Associations were determined between serum anti-CCP2, ACPA fine specificities (vimentin, histone, and alpha-enolase), and IgA, IgG, and IgM RF in pre-RA diagnosis samples and anti-bacterial antibodies using mixed-effects linear regression models.RESULTSNo compelling evidence of case-control divergence in serum anti-P. gingivalis, anti-F. nucleatum, and anti-P. intermedia was observed. Among RA cases, including all pre-diagnosis serum samples, anti-P. intermedia was significantly positively associated with anti-CCP2, ACPA fine specificities targeting vimentin, histone, alpha-enolase, and IgA RF (p<0.001), IgG RF (p = 0.049), and IgM RF (p = 0.004), while anti-P. gingivalis and anti-F. nucleatum were not.CONCLUSIONSNo longitudinal elevations of anti-bacterial serum antibody concentrations were observed in RA patients prior to RA diagnosis compared to controls. However, anti-P. intermedia displayed significant associations with RA autoantibody concentrations prior to RA diagnosis, suggesting a potential role of this organism in progression towards clinically-detectable RA. 1) To quantify the association between anti-Porphyromonas gingivalis serum antibody concentrations and the risk of developing rheumatoid arthritis (RA), and 2) to quantify the associations among RA cases between anti-P. gingivalis serum antibody concentrations and RA-specific autoantibodies. Additional anti-bacterial antibodies evaluated included anti-Fusobacterium nucleatum and anti-Prevotella intermedia. Serum samples were acquired pre- and post- RA diagnosis from the U.S. Department of Defense Serum Repository (n = 214 cases, 210 matched controls). Using separate mixed-models, the timing of elevations of anti-P. gingivalis, anti-P. intermedia, and anti-F. nucleatum antibody concentrations relative to RA diagnosis were compared in RA cases versus controls. Associations were determined between serum anti-CCP2, ACPA fine specificities (vimentin, histone, and alpha-enolase), and IgA, IgG, and IgM RF in pre-RA diagnosis samples and anti-bacterial antibodies using mixed-effects linear regression models. No compelling evidence of case-control divergence in serum anti-P. gingivalis, anti-F. nucleatum, and anti-P. intermedia was observed. Among RA cases, including all pre-diagnosis serum samples, anti-P. intermedia was significantly positively associated with anti-CCP2, ACPA fine specificities targeting vimentin, histone, alpha-enolase, and IgA RF (p<0.001), IgG RF (p = 0.049), and IgM RF (p = 0.004), while anti-P. gingivalis and anti-F. nucleatum were not. No longitudinal elevations of anti-bacterial serum antibody concentrations were observed in RA patients prior to RA diagnosis compared to controls. However, anti-P. intermedia displayed significant associations with RA autoantibody concentrations prior to RA diagnosis, suggesting a potential role of this organism in progression towards clinically-detectable RA. 1) To quantify the association between anti-Porphyromonas gingivalis serum antibody concentrations and the risk of developing rheumatoid arthritis (RA), and 2) to quantify the associations among RA cases between anti-P. gingivalis serum antibody concentrations and RA-specific autoantibodies. Additional anti-bacterial antibodies evaluated included anti-Fusobacterium nucleatum and anti-Prevotella intermedia. Serum samples were acquired pre- and post- RA diagnosis from the U.S. Department of Defense Serum Repository (n = 214 cases, 210 matched controls). Using separate mixed-models, the timing of elevations of anti-P. gingivalis, anti-P. intermedia, and anti-F. nucleatum antibody concentrations relative to RA diagnosis were compared in RA cases versus controls. Associations were determined between serum anti-CCP2, ACPA fine specificities (vimentin, histone, and alpha-enolase), and IgA, IgG, and IgM RF in pre-RA diagnosis samples and anti-bacterial antibodies using mixed-effects linear regression models. No compelling evidence of case-control divergence in serum anti-P. gingivalis, anti-F. nucleatum, and anti-P. intermedia was observed. Among RA cases, including all pre-diagnosis serum samples, anti-P. intermedia was significantly positively associated with anti-CCP2, ACPA fine specificities targeting vimentin, histone, alpha-enolase, and IgA RF (p<0.001), IgG RF (p = 0.049), and IgM RF (p = 0.004), while anti-P. gingivalis and anti-F. nucleatum were not. No longitudinal elevations of anti-bacterial serum antibody concentrations were observed in RA patients prior to RA diagnosis compared to controls. However, anti-P. intermedia displayed significant associations with RA autoantibody concentrations prior to RA diagnosis, suggesting a potential role of this organism in progression towards clinically-detectable RA. [Display omitted] |
ArticleNumber | 152176 |
Author | Edison, Jess D. Feser, Marie L. Robinson, William H. Moss, Laura K. Mikuls, Ted R. Deane, Kevin D. Thiele, Geoffrey M. Wagner, Brandie D. Lee, Joyce A. Kelmenson, Lindsay B. Payne, Jeffrey B. Sayles, Harlan R. |
AuthorAffiliation | a Department of Surgical Specialties, Division of Periodontics, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE, USA c Medicine, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA d Department of Internal Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA h Geriatrics Research Education and Clinical Center, Veterans Affairs Palo Alto Healthcare System and Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA f Department of Internal Medicine, Rheumatology Service, Walter Reed National Military Medical Center, Bethesda, MD, USA b Department of Internal Medicine, Division of Rheumatology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA e Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE USA g Department of Biostatistics and Informatics, School of Public Health, University of Col |
AuthorAffiliation_xml | – name: a Department of Surgical Specialties, Division of Periodontics, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE, USA – name: c Medicine, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA – name: e Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE USA – name: d Department of Internal Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – name: h Geriatrics Research Education and Clinical Center, Veterans Affairs Palo Alto Healthcare System and Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA – name: g Department of Biostatistics and Informatics, School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – name: b Department of Internal Medicine, Division of Rheumatology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA – name: f Department of Internal Medicine, Rheumatology Service, Walter Reed National Military Medical Center, Bethesda, MD, USA |
Author_xml | – sequence: 1 givenname: Joyce A. surname: Lee fullname: Lee, Joyce A. organization: Department of Surgical Specialties, Division of Periodontics, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE, USA – sequence: 2 givenname: Ted R. surname: Mikuls fullname: Mikuls, Ted R. organization: Department of Internal Medicine, Division of Rheumatology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA – sequence: 3 givenname: Kevin D. surname: Deane fullname: Deane, Kevin D. organization: Department of Internal Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – sequence: 4 givenname: Harlan R. surname: Sayles fullname: Sayles, Harlan R. organization: Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE USA – sequence: 5 givenname: Geoffrey M. surname: Thiele fullname: Thiele, Geoffrey M. organization: Department of Internal Medicine, Division of Rheumatology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA – sequence: 6 givenname: Jess D. surname: Edison fullname: Edison, Jess D. organization: Department of Internal Medicine, Rheumatology Service, Walter Reed National Military Medical Center, Bethesda, MD, USA – sequence: 7 givenname: Brandie D. surname: Wagner fullname: Wagner, Brandie D. organization: Department of Biostatistics and Informatics, School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – sequence: 8 givenname: Marie L. surname: Feser fullname: Feser, Marie L. organization: Department of Internal Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – sequence: 9 givenname: Laura K. surname: Moss fullname: Moss, Laura K. organization: Department of Internal Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – sequence: 10 givenname: Lindsay B. surname: Kelmenson fullname: Kelmenson, Lindsay B. organization: Department of Internal Medicine, Division of Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – sequence: 11 givenname: William H. surname: Robinson fullname: Robinson, William H. organization: Geriatrics Research Education and Clinical Center, Veterans Affairs Palo Alto Healthcare System and Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA – sequence: 12 givenname: Jeffrey B. orcidid: 0000-0001-9920-7746 surname: Payne fullname: Payne, Jeffrey B. email: jbpayne@unmc.edu organization: Department of Surgical Specialties, Division of Periodontics, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE, USA |
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Keywords | Porphyromonas gingivalis Rheumatoid factor Periodontitis Prevotella intermedia ACPA Rheumatoid arthritis |
Language | English |
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development of rheumatoid arthritis publication-title: Inflammation doi: 10.1007/s10753-004-6641-z contributor: fullname: Rosenstein – volume: 64 start-page: 3522 issue: 11 year: 2012 ident: 10.1016/j.semarthrit.2023.152176_bib0014 article-title: Porphyromonas gingivalis and disease-related autoantibodies in individuals at increased risk of rheumatoid arthritis publication-title: Arthritis Rheum doi: 10.1002/art.34595 contributor: fullname: Mikuls |
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Snippet | 1) To quantify the association between anti-Porphyromonas gingivalis serum antibody concentrations and the risk of developing rheumatoid arthritis (RA), and 2)... OBJECTIVES1) To quantify the association between anti-Porphyromonas gingivalis serum antibody concentrations and the risk of developing rheumatoid arthritis... |
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SubjectTerms | ACPA Antibodies, Bacterial Arthritis, Rheumatoid Autoantibodies Case-Control Studies Histones Humans Immunoglobulin A Immunoglobulin G Immunoglobulin M Periodontitis Phosphopyruvate Hydratase Porphyromonas gingivalis Prevotella intermedia Rheumatoid arthritis Rheumatoid Factor Vimentin |
Title | Serum antibodies to periodontal pathogens prior to rheumatoid arthritis diagnosis: A case-control study |
URI | https://dx.doi.org/10.1016/j.semarthrit.2023.152176 https://www.ncbi.nlm.nih.gov/pubmed/36812865 https://www.proquest.com/docview/2779349748/abstract/ https://pubmed.ncbi.nlm.nih.gov/PMC10243205 |
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