Porphyromonas Gingivalis and the Pathogenesis of Rheumatoid Arthritis: Analysis of the Synovial Tissue and of Other Compartments

Background/Purpose: Porphyromonas gingivalis (Pg), a periodontal anaerobic intracellular pathogen, has been recently associated to rheumatoid arthritis (RA) and the pathogenesis of the disease, due to its unique characteristic of citrullinating host and bacterial peptides. Given the mainly intracellular life of the bacterium, the aim of the study was to evaluate the presence of Pg DNA in the synovial tissue (ST) of RA patients through synovial biopsy in comparison with patients affected by other arthritides. Possible links with clinical, immunologic and genetic features were assessed. Methods: Peripheral blood (PB), sub-gingival dental plaque, synovial fluid (SF) and ST samples were collected from 69 patients with active knee arthritis (32 with RA and 37 with other arthritides, of which 14 with 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. Results: No 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 HLA DRB1*04 allele showed a higher positivity for Pg DNA in the ST 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 leucocytes and neutrophils count. The presence of Pg DNA did not influence disease activity, disease disability or positivity for autoantibodies. Conclusion: The 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, thus contributing to the loss of tolerance, in particular in patients positive for HLA-DR4.