Porphyromonas gingivalis and disease-related autoantibodies in individuals at increased risk of rheumatoid arthritis

Ted R Mikuls, Geoffrey Milton Thiele, Kevin D. Deane, Jeffrey B Payne, James Robert O'Dell, Fang Yu, Harlan Sayles, Michael H. Weisman, Peter K. Gregersen, Jane H. Buckner, Richard M. Keating, Lezlie A. Derber, William H. Robinson, V. Michael Holers, Jill M. Norris

Research output: Contribution to journalArticle

128 Scopus citations

Abstract

Objective To examine the relationship of Porphyromonas gingivalis to the presence of autoantibodies in individuals at risk of rheumatoid arthritis (RA). Methods Study participants included the following: 1) a cohort enriched in subjects with HLA-DR4 and 2) subjects at risk of RA by virtue of having a first-degree relative with RA. None of the study subjects satisfied the American College of Rheumatology 1987 classification criteria for RA. Autoantibodies measured included anti-citrullinated protein antibody (ACPA; by second-generation anti-cyclic citrullinated peptide antibody enzyme-linked immunosorbent assay [ELISA]) and rheumatoid factor (RF; by nephelometry or ELISA for IgA, IgM, or IgG isotype). Individuals were considered autoantibody positive (n = 113) if they had ≥1 RA-related autoantibody; individuals were further categorized as high risk (n = 38) if they had ACPA or positive findings ≥2 assays for RF. Autoantibody-negative individuals (n = 171) served as a comparator group. Antibody to P gingivalis, P intermedia, and F nucleatum were measured. Associations of bacterial antibodies with group status were examined using logistic regression. Results Anti-P gingivalis concentrations were higher in high-risk (P = 0.011) and autoantibody positive group (P = 0.010) than in the autoantibody negative group. There were no group differences in anti-P intermedia or anti-F nucleatum concentrations. After multivariable adjustment, anti-P gingivalis concentrations (but not anti-P intermedia or anti-F nucleatum) were significantly associated with autoantibody-positive and high-risk status (P < 0.05). Conclusion Immunity to P gingivalis, but not P intermedia or F nucleatum, is significantly associated with the presence of RA-related autoantibodies in individuals at risk of RA. These results support the hypothesis that infection with P gingivalis may play a central role in the early loss of tolerance to self antigens that occurs in the pathogenesis of RA.

Original languageEnglish (US)
Pages (from-to)3522-3530
Number of pages9
JournalArthritis and rheumatism
Volume64
Issue number11
DOIs
StatePublished - Nov 1 2012

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Mikuls, T. R., Thiele, G. M., Deane, K. D., Payne, J. B., O'Dell, J. R., Yu, F., Sayles, H., Weisman, M. H., Gregersen, P. K., Buckner, J. H., Keating, R. M., Derber, L. A., Robinson, W. H., Holers, V. M., & Norris, J. M. (2012). Porphyromonas gingivalis and disease-related autoantibodies in individuals at increased risk of rheumatoid arthritis. Arthritis and rheumatism, 64(11), 3522-3530. https://doi.org/10.1002/art.34595