Porphyromonas gingivalis Triggers Clinical Autoimmune Arthritis in HLA/DR1 Collagen-Induced-Arthritis-Resistant Mice

Objectives: To determine whether Porphyromonas gingivalis (Pg) can trigger clinical autoimmune arthritis in mice bearing a human HLA/DR1 allele that were resistant to collagen-induced arthritis (CIA). Pg is an anaerobic Gram-(negative) bacterium implicated in the pathogenesis of periodontitis and recently of Rheumatoid Arthritis (RA), a chronic inflammatory disease characterized by joint soft tissue and bone destruction. Pg expresses a peptidyl-arginine deiminase (PAD) responsible for host protein citrullination and production of anti-citrullinated protein antibodies (ACPAs), hypothesized to trigger autoimmunity and characteristic for RA disease activity. Autoimmune arthritis is commonly studied in mice bearing the HLA/DR1 allele (“shared epitope” SE that increases the risk for RA in humans) challenged with bovine type II collagen emulsified in Complete Freund’s Adjuvant (CFA), but 5-10% of the challenged mice do not develop clinical signs of arthritis.
Methods: Nine C57BL/6 mice bearing the human major histocompatibility complex allele DRB*0101 as a transgene and null for the murine class II, that were challenged with collagen II in CFA but did not develop clinical arthritis 75 days post-treatment were used for this study. Five mice were inoculated orally with Pg for seven days, while four remained untreated. The incidence, severity and paw index for clinical arthritis were calculated.
Results: Infection of periodontal tissues by Pg was confirmed by PCR. All mice inoculated with Pg developed clinical arthritis within 10 days from initiation of Pg-treatment (100% for Pg-treated group, 0% for controls, p<0.05). Arthritis severity in the Pg-treated group reached of 6.8 and paw index reached 1.8, whereas these values remained zero in the untreated group (p<0.05).
Conclusions: Our preliminary data indicate that autoimmune inflammatory response and induction of clinical arthritis may be triggered by Pg infection in mice previously resistant to the development of clinical autoimmune arthritis, by tipping the immune response balance towards overt an overt arthritic phenotype.