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.
Chronic periodontitis is an inflammatory disease of the periodontium affecting nearly 65 million adults in the United States. Changes in subgingival microbiota have long been associated with chronic periodontitis. Recent culture-independent molecular studies have revealed the immense richness and complexity of oral microbial communities. However, data sets across studies have not been directly compared, and whether the observed microbial variations are consistent across different studies is not known. Here, we used 16S rRNA sequencing to survey the subgingival microbiota in 25 subjects with chronic periodontal disease and 25 healthy controls and compared our data sets with those of three previously reported microbiome studies. Consistent with data from previous studies, our results demonstrate a significantly altered microbial community structure with decreased heterogeneity in periodontal disease. Comparison with data from three previously reported studies revealed that subgingival microbiota clustered by study. However, differences between periodontal health and disease were larger than the technical variations across studies. Using a prediction score and applying five different distance metrics, we observed two predominant clusters. One cluster was driven by Fusobacterium and Porphyromonas and was associated with clinically apparent periodontitis, and the second cluster was dominated by Rothia and Streptococcus in the majority of healthy sites. The predicted functional capabilities of the periodontitis microbiome were significantly altered. Genes involved in bacterial motility, energy metabolism, and lipopolysaccharide biosynthesis were overrepresented in periodontal disease, whereas genes associated with transporters, the phosphotransferase system, transcription factors, amino acid biosynthesis, and glycolysis/gluconeogenesis were enriched in healthy controls. These results demonstrate significant alterations in microbial composition and function in periodontitis and suggest genes and metabolic pathways associated with periodontal disease. P eriodontal disease is a common disease affecting many adults in the United States. If left untreated, chronic periodontitis (CP) can lead to serious problems such as tooth loss. Indeed, periodontal disease is the number one cause of tooth loss in the United States, accounting for half of all tooth loss in U.S. adults (1). 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 (6-8), and rheumatoid arthritis (9-11).The activity of periodontal disease is determined by a complex interplay between the immune system and periodontal pathogens (12, 13). Alterations in subgingival microbiota have long been associated with the development and progression of periodontitis (14). In susceptible individuals, perturbations in...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.