Rheumatoid Arthritis (RA) is a chronic disorder characterized by a frequently disabling erosive arthritis. The etiopathogenesis of the disease is still only partly understood and no biomarkers with good sensitivity and specificity for diagnostic and prognostic evaluations are available nowadays. During the last years, experimental evidences of a correlation between development of RA and parodontal inflammatory disease, mainly from microbial infections, as Porphyromonas Gingivalis (PG) or Aggregatibacter actinomycetemcomitans (Aa), have grown. This research project aims to evaluate whether new disease biomarkers might be indentified from the study of parodontopathy associated with RA. In particular, it is tempting to investigate if infections from pathogens liable for the main parodontitis (PD), might be able to activate the main processes of cellular response, including autophagy, and cell NETosis, with a relationship with the production of specific biomarkers. The project will enroll patients suffering from RA and healthy subjects to undergo parodontal examination, PG/Aa isolation from gingival lesions and lingual biofilm. It will be investigated the ability in inducing post-translational modifications (citrullination, carbamylation) that can be related to the production of autoantibodies (anti-citrullinated/carbamylated protein antibodies, ACPA/anti-CarP). The purified and characterized microbial material will be also used to study the ability to induce autophagy and cell NETosis. In addition, we aim to directly determinate the involvement of alarmins, such as HMGB1, for the induction of synovial hyperplasia and chronic inflammation. From the molecular study of the pathogenetic mechanism we could identify new therapeutic targets to invest in the future of RA therapies. These new pathogenic aspects could have consequences in clinical practice, in terms of have therapeutic and preventive implications, but also on the discovery of new biomarkers.
The increase of knowledge about some RA pathogenic mechanisms potentially resulting from the present study might represent an innovative approach for the discovery of new biomarkers, deriving from a multidisciplinary modality. The individuation of these biomarkers involves characteristics and peculiarities of oral pathogens, their enzymatic machinery, results of their interaction with host immune response, as well as specific features of cell biology (activation, starvation, death, etc.). Our project could have clinical implications, in terms of diagnosis, prognosis and response to treatment. Thus, biomarkers individuated through the studies and experiments of this project might have been validated on larger clinical studies accordingly to specific therapeutic protocols. The possible role of these biomarkers as prognostic factors in terms of treatment response could be very interesting also in terms of pharmaco-economy, in order to allow a rationalization of the health care costs. With regard to this last aspect, it is noteworthy to mention that the new and effective treatments of RA, with the employment of biologic drugs, are beset by the huge costs.