Periodontitis and Porphyromonas gingivalis in Patients With Rheumatoid Arthritis

Abstract

Purpose To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) with rheumatoid arthritis (RA) and to examine associations of PD and Porphyomonas gingivalis (Pg) with disease features. Methods RA cases (N=287) and controls (N=330) underwent a standardized periodontal examination. HLA-DRB1 status was imputed using SNPs from the extended MHC. Circulating anti-Pg antibody was measured using ELISA and subgingival plaque was assessed for the presence of Pg using PCR. Associations of PD with RA were examined using multivariable regression. Results PD was more common in RA (35%, p = 0.022) and aCCP positive RA (n=240; 37%; p = 0.006) vs. controls (26%). There were no RA-control differences in anti-Pg or the frequency of Pg positivity by PCR. Anti-Pg antibody showed weak but statistically significant associations with both anti-CCP (r=0.14, p=0.022) and RF (r=0.19, p=0.001). PD was associated with increased swollen joint counts (p=0.004), DAS-28-CRP (p=0.045), total Sharp scores (p=0.015), aCCP (p=0.011), and RF (p<0.001). Select anti-citrullinated peptide antibody (ACPA; including antibody to citrullinated filaggrin) were higher in patients with subgingival Pg and higher anti-Pg antibody levels irrespective of smoking. Associations of PD with established seropositive RA were independent of all covariates examined including evidence of Pg infection. Conclusions Both PD and Pg appear to shape RA-related autoreactivity in RA. In addition, PD demonstrates an independent relationship with established seropositive RA.

Dysbiosis and Alterations in Predicted Functions of the Subgingival Microbiome in Chronic Periodontitis

“…There is considerable evidence that the clinical impact of periodontal disease extends beyond the oral cavity (2). Strong associations have been found between periodontitis and a number of systemic conditions, including cardiovascular disease (3,4), preterm delivery and low-birth-weight babies (5), diabetes mellitus (6)(7)(8), and rheumatoid arthritis (9)(10)(11).…”

Review: Preclinical Rheumatoid Arthritis: Progress Toward Prevention

“…The observation that patients without RA who have PD have higher serum ACPA levels and anti-P gingivalis levels compared to those who do not have PD (20,21) lends further support to this hypothesis. This holds true in established RA, where the association between PD and RA appears to be restricted to ACPA-positive patients (22). Localized ACPA responses at the oral mucosa have also been described; IgA anti-cyclic citrullinated peptide (anti-CCP) antibodies have been reported in the saliva of RA patients (23) and IgG anti-CCP antibodies have been reported in the gingival crevicular fluid of patients with PD (24).…”

Smoking and Air Pollution as Pro-Inflammatory Triggers for the Development of Rheumatoid Arthritis

“…Porphyromonas gingivalis, the major causative pathogen in chronic periodontitis, possesses a bacterial PAD which is capable of citrullinating both host and bacterial proteins, potentially triggering the generation of ACPA in genetically predisposed individuals. Not surprisingly, the prevalence of RA is increased in patients with P. gingivalis -associated chronic periodontitis, which correlates with circulating levels of ACPA [45,46]. Citrullination of periodontal proteins such as filaggrin, vimentin and enolase, as well as bacterial antigens, results in a range of different ACPA specificities with antibodies to citrullinated enolase peptides most strongly associated with RA [47].…”