Background

Periodontitis is the most prevalent infectious inflammatory disease of mankind. It is estimated that up 30% of the adult population suffers from periodontitis and in approximately 8%, a severe form of the disease ultimately leads to tooth loss. If morbidity caused by tooth loss due to advanced periodontitis is not enough, mounting evidence suggests a causative link between periodontal disease and rheumatoid arthritis, as well as between periodontitis and cardiovascular disease.

Rheumatoid arthritis (RA), affecting 0.5-1% worldwide, is a severe systemic autoimmune disease, where patients suffer chronic joint inflammation, causing pain and disability, comorbidities and increased mortality. Autoimmunity in rheumatoid arthritis (RA) is characterised by an antibody response to citrullinated proteins. Periodontitis (PD) is largely caused by infection, in which Porphyromonas gingivalis is a major pathogen.

The two diseases combine specific HLA-DRB1alleles and smoking as risk factors, and have a similar pathophysiology characterised by destructive inflammation. A possible causative link between RA and PD is based on the ability of P. gingivalis to citrullinate proteins and thereby generate autoantigens that drive autoimmunity in RA. We hypothesise that anti-citrullinated protein antibodies can be generated, in genetically susceptible individuals, as a consequence of P.gingivalis-induced citrullination in the gingiva. In the context of genetic risk factors, during chronic exposure to danger signals, such as bacterial lipopolysacharides and DNA, tolerance to citrullinated proteins may be broken, with production of a pathogenic antibody response, which at a later time point cross-reacts with joint proteins and causes chronic RA. In our project we will use a multidisciplinary approach (genetics, epidemiology, molecular immunology and animal models) to study susceptibility factors and immune responses in RA and PD, with an aim to identify novel etiological and pathogenic pathways, forming the basis for new therapies.