Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2019 Jun 5;2(6):e195394.
doi: 10.1001/jamanetworkopen.2019.5394.

Prevalence of Periodontal Disease and Periodontopathic Bacteria in Anti-Cyclic Citrullinated Protein Antibody-Positive At-Risk Adults Without Arthritis

Kulveer Mankia  1   2 , Zijian Cheng  3 , Thuy Do  3 , Laura Hunt  1   2 , Josephine Meade  3 , Jing Kang  3 , Val Clerehugh  4 , Alastair Speirs  4 , Aradhna Tugnait  4 , Elizabeth M A Hensor  1 , Jackie L Nam  1   2 , Deirdre A Devine  3 , Paul Emery  1   2
Affiliations
Observational Study

Prevalence of Periodontal Disease and Periodontopathic Bacteria in Anti-Cyclic Citrullinated Protein Antibody-Positive At-Risk Adults Without Arthritis

Kulveer Mankia et al. JAMA Netw Open. .

Abstract

Importance: The prevalence of periodontitis is increased in patients with rheumatoid arthritis (RA) and periodontopathic bacteria can citrullinate proteins. Periodontitis may, therefore, be an initiator of RA and a target for prevention. Periodontal disease and periodontal bacteria have not been investigated in at-risk individuals with RA autoimmunity but no arthritis.

Objective: To examine periodontal disease and periodontopathic bacteria in anti-cyclic citrullinated protein (anti-CCP) antibody-positive at-risk individuals without arthritis.

Design, setting, and participants: This cross-sectional study took place at a teaching hospital from April 27, 2015, to May 8, 2017. Forty-eight anti-CCP-positive individuals without arthritis (CCP+ at-risk) were recruited nationally. Twenty-six patients with early RA (ERA) and 32 healthy control individuals were recruited locally. Data were analyzed between June 1, 2017, and December 1, 2017.

Interventions: Periodontal assessment and examination of joints using ultrasonography.

Main outcomes and measures: Prevalence of diseased periodontal sites, clinical periodontitis, and periodontal inflamed surface area in CCP+ at-risk individuals compared with patients with ERA and healthy individuals matched for age and smoking. Paired-end sequencing of DNA from subgingival plaque from diseased and healthy periodontal sites was performed and DNA was profiled and analyzed.

Results: A total of 48 CCP+ at-risk individuals (mean [SD] age, 51.9 [11.4] years; 31 [65%] female), 26 patients with ERA (mean [SD] age, 54.4 [16.7] years; 14 [54%] female), and 32 healthy individuals (mean [SD] age, 49.4 [15.3] years; 19 [59%] female) were recruited. Of 48 CCP+ at-risk individuals, 46 had no joint inflammation on ultrasonography. Thirty-five CCP+ at-risk individuals (73%), 12 healthy individuals (38%), and 14 patients with ERA (54%) had clinical periodontitis. The median (interquartile range) percentage of periodontal sites with disease was greater in CCP+ at-risk individuals compared with healthy individuals (3.3% [0%-11.3%] vs 0% [0%-0.7%]) and similar to patients with ERA (1.1% [0%-13.1%]). Median (interquartile range) periodontal inflamed surface area was higher in CCP+ at-risk individuals compared with healthy individuals (221 mm2 [81-504 mm2] vs 40 mm2 [12-205 mm2]). Patients with CCP+ at-risk had increased relative abundance of Porphyromonas gingivalis (but not Aggregatibacter actinomycetemcomitans) at healthy periodontal sites compared with healthy individuals (effect size, 3.00; 95% CI, 1.71-4.29) and patients with ERA (effect size, 2.14; 95% CI, 0.77-3.52).

Conclusions and relevance: This study found increased prevalence of periodontitis and P gingivalis in CCP+ at-risk individuals. This suggests periodontitis and P gingivalis are associated with disease initiation and could be targets for preventive interventions in RA.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Mankia reported grants from the National Institute for Health Research (NIHR) Leeds Biomedical Research Unit and grants from Leeds Biomedical Research Centre during the conduct of the study. Dr Tugnait reported grants from the Leeds Biomedical Research Centre during the conduct of the study. Dr Hensor reported grants from the NIHR during the conduct of the study and grants from Arthritis Research UK outside the submitted work. Dr Devine reported grants from NIHR, the China Scholarship Council, and the Wellcome Trust during the conduct of the study; and grants from Colgate Palmolive Inc and Glaxo SmithKline, and grants and personal fees from ADM Protexin Ltd outside the submitted work. Dr Emery reported grants and personal fees from Pfizer, Merck Sharp & Dohme, AbbVie, Bristol-Myers Squibb, Roche, Samsung, Sandoz, and Eli Lilly and Company; and personal fees from Novartis and UCB outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Abundance of Periodontal Bacteria at Diseased and Healthy Dental Sites According to Rheumatoid Arthritis (RA) Status
The abundance of Aggregatibacter actinomycetemcomitans, Filifactor alocis, and Porphyromonas gingivalis compared between groups using the Wald test. CCP+ indicates individuals positive for anti–cyclic citrullinated peptide antibodies; HC, healthy control. aAdjusted P value <.001. bAdjusted P value <.05.
See this image and copyright information in PMC

Comment in

References

    1. Nielen MM, van Schaardenburg D, Reesink HW, et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004;50(2):-. doi: 10.1002/art.20018 - DOI - PubMed
    1. Brink M, Hansson M, Mathsson L, et al. Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis. Arthritis Rheum. 2013;65(4):899-910. doi: 10.1002/art.37835 - DOI - PubMed
    1. van de Sande MG, de Hair MJ, van der Leij C, et al. Different stages of rheumatoid arthritis: features of the synovium in the preclinical phase. Ann Rheum Dis. 2011;70(5):772-777. doi: 10.1136/ard.2010.139527 - DOI - PubMed
    1. Barra L, Scinocca M, Saunders S, et al. Anti-citrullinated protein antibodies in unaffected first-degree relatives of rheumatoid arthritis patients. Arthritis Rheum. 2013;65(6):1439-1447. doi: 10.1002/art.37911 - DOI - PubMed
    1. Ärlestig L, Mullazehi M, Kokkonen H, Rocklöv J, Rönnelid J, Dahlqvist SR. Antibodies against cyclic citrullinated peptides of IgG, IgA and IgM isotype and rheumatoid factor of IgM and IgA isotype are increased in unaffected members of multicase rheumatoid arthritis families from northern Sweden. Ann Rheum Dis. 2012;71(6):825-829. doi: 10.1136/annrheumdis-2011-200668 - DOI - PMC - PubMed

Publication types

MeSH terms

Substances