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

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.

A molecular signature of preclinical rheumatoid arthritis triggered by dysregulated PTPN22

“…Porphyromonas gingivalis, the most common pathogen of periodontitis, expresses a PAD-like enzyme that is capable of citrullinating host proteins (6,7). Several epidemiological studies have suggested an association between periodontitis and risk of developing ACPA or RA (8)(9)(10). In addition, a functional haplotype stabilizing the mRNA from padi4, the gene encoding PAD4, is associated with a higher risk of RA and the presence of ACPA in RA patients (11)(12)(13)(14).…”

Periodontal Pathogens Directly Promote Autoimmune Experimental Arthritis by Inducing a TLR2- and IL-1–Driven Th17 Response

“…Other studies showed a reduction of the severity of active RA when the accompanying PD was successfully treated (15,16). In addition, enhanced Ab titers against Porphyromonas gingivalis, the major causative agent of periodontitis, have been detected in serum of patients with RA as well as in individuals at increased risk of developing RA (17,18).…”

Review: Preclinical Rheumatoid Arthritis: Progress Toward Prevention

“…Additionally, there is evidence that PAD auto- No difference found in anti-P gingivalis levels between RA patients and controls. Mikuls et al (68) Anti-P gingivalis antibodies Higher levels of anti-P gingivalis antibodies in at-risk individuals with RA autoantibodies compared to those seronegative for autoantibodies. Lappin et al (21) Anti-CCP antibodies Patients with PD had higher anti-CCP levels than healthy controls; significant reductions in anti-CCP and anti-P gingivalis titers seen after PD treatment.…”