Protein citrullination as a link between periodontal diseases and rheumatoid arthritis (RA) and target for development of novel drugs to treat RA.
Coordinator: Piotr MYDEL
Project Number: 261460
EC contribution: € 5,851,588.00
Project website: http://gumsandjoints.com
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. 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.