Chronic periodontitis is one of the most frequently occurring chronic inflammatory disease, it can affect even around 50% of adult population. The outcome of the sustained inflammatory state is gradual destruction of periodontal tissue and finally tooth loss. The currently established model of the disease progression is based on bacterial species Porphyromonas gingivalis, which produces virulence factors prolonging inflammatory reaction of the organism. At the same time the antibacterial factors of the immune system are inactivated allowing the pathological state to continue and the uncontrolled overgrowth of bacterial microflora.

One of such virulence factors is peptidylarginine deiminase (PPAD) which converts terminal arginine in proteins and peptides to neutral citrulline. Such modification can change the structure and therefore function of modified substrate, in this way regulatory factors of inflammation and healing process are inactivated in the gums. Citrullination is a key process in another inflammatory disease, rheumatoid arthritis. The factor leading to the disease is initiation of pathologic inflammatory reaction of the organism and production of anti citrullinated peptides antibodies (ACPA). The connection between periodontitis and rheumatoid arthritis was observed in many studies reporting the cooccurrence of those diseases, also risk factors like smoking are similar in both conditions.

The exact mechanism connecting those disease is not yet proven, however a promising hypothesis is the activation of immune reaction by citrullinated peptides produced during the inflammatory process in the gums. The current project aims to investigate the effect of PPAD and citrullinated P. gingivalis proteins on the progression of periodontitis and the potential ability of this enzyme to mediate the onset of ACPA. To accomplish this we will investigate the effect of total citrullinated proteins on the surface of P. gingivalis and identified modified proteins on production of inflammatory factors by gingival fibroblasts. This will explain the mechanism of recognition of modified peptides by gum cells and their effect on sustaining the inflammatory state. Next, we will test the possibility of PPAD acting as a carrier of citrullinated peptides into cells of the immune system, which then present such peptides and lead to production of antibodies against them.

Showing such mechanism would explain the key stage leading to ACPA production. It was observed that PPAD can occur in two forms, which differ in the level of enzymatic activity. Using clinical material from periodontitis and rheumatoid arthritis patients we will investigate the correlation between occurrence of the more active PPAD and frequency of the diseases.

Results obtained by this project will help answer key questions, explaining the missing element connecting periodontitis and rheumatoid arthritis. It will also allow new approach to prevention and treatment of those diseases.