A recent study published in the PLoS Pathogens, a scientific journal, reveals that a bacterium Porphyromonas gingivalis is responsible for periodontal disease. Interestingly, the bacterium also worsens rheumatoid arthritis by leading to earlier onset and faster disease progression.
Periodontal disease (PD) and Rheumatoid arthritis (RA) are two known chronic inflammatory diseases, whose association has been hinted at, but the mechanisms have been unclear- especially when it comes to microbial connection.
Comparing PD and RA
Jan Potempa, group researcher at School of Dentistry Oral Health and Systemic Disease (University of Louisville), has found that RA is worsened by P.gingivalis and PD’s bacterium is responsible for it. This response leads to the destruction of supporting structures of the teeth.
Dr. Sherri Worth, an expert in reconstructive dentistry, has also reported significant work on such deformities. While her work has been mostly to improve the quality of life aspect of PD, it gives decent insight into the varying levels of deformities in dentine structures. This study would also help to bring improvement in esthetic & reconstructive dentistry.
As opposed to PD, RA is an autoimmune disorder defined by chronic inflammation that damages bone and cartilage within joints. Antibodies against citrullinated proteins are important as biomarkers that can detect the onset of the disease and also verify its severity.
The Mechanism Unraveled
The process of protein citrullination is carried out by enzymes known as peptidyl-arginine deiminases (PADs). The PAD catalyzed protein citrullination has been known to occur at the time of pathological inflammation. It leads to breakdown of immune tolerance and lead to induction of RA.
There is a lot of clinical evidence that individuals with PD have more prevalence of RA, and vice versa. In fact, one study showed that PD is nearly 2 fold more prevalent in RA patients.
This study done at the University of Louisville School of Dentistry Oral Health and Systemic Diseases, aimed at checking the hypothesis if P.gingivalis produces PAD enzyme that has a profound impact on the development and progression of RA through the citrullination of proteins that form neo-epitopes.
The researchers were able to show that infection with viable periodontal pathogen Porphyromonas gingivalis strain W83 caused collagen induced arthritis (CIA) in a mouse model. This was defined by earlier onset, accelerated progression and enhanced severity of the disease, including significantly increased bone and cartilage destruction.
The researchers also reported that CIA augmenting ability of P.gingivalis was related to the expression of the peptidyl arginine deiminase enzyme (PPAD). This converted the arginine resides present in proteins to citrulline.
It was also verified that that when infection was done with the wild type P.gingivalis, there were increased levels of auto-antibodies detected against collage type 2 and citrullinated epitopes. The PPAD null mutant couldn’t produce the same host response, proving the validity of the hypothesis. Also, PAD non-producing bacteria, Prevotella intermedia were also checked, but didn’t affect CIA.
The high level of citrullinated proteins at the site of infection with wild type P.gingivalis showed that the bacterial PAD was the ‘mechanism link’ between the periodontal infection and rheumatoid arthritis.
Therefore, the findings provide good inroads to the link between PD and RA. Also, the site of infection can be taken as a common ground for some therapeutic intervention. This is one area where researchers can further focus on.