Porphyromonas gingivalis and the pathogenesis of rheumatoid arthritis: analysis of various compartments including the synovial tissue

Abstract

IntroductionWe evaluated the presence of Porphyromonas gingivalis (Pg) DNA in the synovial tissue through synovial biopsy and in other compartments of rheumatoid arthritis (RA) patients in comparison with patients affected by other arthritides. Possible links with clinical, immunologic and genetic features were assessed.MethodsPeripheral blood (PB), sub-gingival dental plaque, synovial fluid (SF) and synovial tissue samples were collected from 69 patients with active knee arthritis (32 with RA and 37 with other arthritides, of which 14 had undifferentiated peripheral inflammatory arthritis - UPIA). Demographic, clinical, laboratory and immunological data were recorded. The presence of Pg DNA was evaluated through PCR. The HLA-DR haplotype was assessed for 45 patients with RA and UPIA.ResultsNo differences arose in the positivity for Pg DNA in the sub-gingival plaque, PB and SF samples between RA and the cohort of other arthritides. Full PB samples showed a higher positivity for Pg DNA than plasma samples (11.8% vs. 1.5%, P = 0.04). Patients with RA showed a higher positivity for Pg DNA in the synovial tissue compared to controls (33.3% vs. 5.9%, P <0.01). UPIA and RA patients carrying the HLA DRB1*04 allele showed a higher positivity for Pg DNA in the synovial tissue compared to patients negative for the allele (57.1% vs. 16.7%, P = 0.04). RA patients positive for Pg DNA in the sub-gingival plaque had a lower disease duration and a higher peripheral blood leucocyte and neutrophil count. The presence of Pg DNA did not influence disease activity, disease disability or positivity for autoantibodies.ConclusionsThe presence of Pg DNA in the synovial tissue of RA patients suggests a pathogenic role of the bacterium. The higher positivity of Pg DNA in full peripheral blood and synovial tissue samples compared to plasma and synovial fluid suggests a possible intracellular localization of Pg, in particular in patients positive for HLA-DR4.

Effects by periodontitis on pristane-induced arthritis in rats

“…Using that technique, we were able to confirm the presence of P. gingivalis DNA in ligatures from all 9 challenged animals (Additional file 1: Figure S1a, b). Due to the fact that the presence of P. gingivalis DNA in synovial tissue of patients with active periodontitis have previously been reported [43], we also tested DNA isolated from metacarpophalangeal joint tissue of challenged animals. However, we were not able to detect any traces of P. gingivalis in these samples (data not shown).…”

“…The oral pathogen P. gingivalis , strongly associated with periodontitis, has been suggested to be involved in the pathogenesis of RA since the presence of P. gingivalis DNA has previously been reported in the synovial tissue of RA patients [43], and since patients with RA have been shown to have higher anti- P. gingivalis and anti-RgpB antibody levels, compared to controls [26, 30]. In the current study, in line with previously reported data [68] P. gingivalis DNA was detected in the oral cavity of the periodontitis-affected animals, although the presence of P. gingivalis in metacarpophalangeal joint tissue of periodontitis-affected animals could not be detected.…”

Genome Sequence of Porphyromonas gingivalis Strain 381

“…Porphyromonas gingivalis is an anaerobic bacterium (1) that is linked with periodontal disease (2–4) and multiple systemic diseases (5–7). In previous studies (8–11), P. gingivalis strains have shown a variety of pathogenic phenotypes in vitro and in vivo , but underlying genetic mechanisms are poorly defined.…”

Prelude to oral microbes and chronic diseases: past, present and future

“…Joint problems have been correlated with oral diseases to our knowledge since the time of Hippocrates, but the association of periodontal disease, and specifically Porphyromonas gingivalis, with rheumatoid arthritis is much more recent [53]. This association is also to date perhaps one of the most studied oral versus systemic chronic disease links [53, 54]. Multiple epidemiologic and clinical studies have found varying relations between periodontal disease and RA [10, 53].…”

“…As players in the etiology of periodontal disease, several oral bacteria have been studied for association with RA etiology. Clinical studies have detected P. gingivalis, Prevotella intermedia , and Prevotella nigrescens DNA in sera and synovial fluids of RA patients [56], and antibodies against P. gingivalis, A. actinomycetemcomitans and few other oral microbiota constituents have also been found in sera of patients suffering from RA, compared to healthy controls [53, 54]. …”