Periodontitis and Rheumatoid Arthritis - Association, Dual Treatment and Resolution

Abstract

Rheumatoid arthritis (RA) and periodontitis (PD) are prevalent chronic conditions associated with significant morbidity. Both conditions are characterized by chronic inflammation and local tissue destruction. Evidence from our and other groups indicates that RA and PD not only often concur, but may also have a shared etiopathogenesis. The production of inflammatory and microbial particles during PD may enhance arthritogenic immune activation. Furthermore, PD may induce a break in immune tolerance in genetically predisposed individuals, resulting in production of the RA-defining anti-citrullinated peptide antibodies (ACPA) and elevated Th17 subset responses. It is clinically highly relevant to investigate whether RA disease activity can be diminished by oral treatment of PD. Thus, the aim of this study will be establish and validate a novel combined model for chronic, progressive arthritis and periodontitis, aimed at closely mimicking human RA and PD using the rice rat model, and chronic adjuvant arthritis. To gain further insight into the interconnection of the two disease models at the immunological level, ACPA levels will be determined, T lymphocytes from spleen, draining and non-draining lymph nodes will be isolated, their responsiveness to various antigens investigated, and T cell subsets analyzed by flowcytometry. Subsequently, this model will be validated with current anti-rheumatic drugs such as anti-TNF treatment. Our next objective is to test the feasibility and efficacy of a new dual treatment modality for PD and RA using biomaterials for sustained local delivery. For this purpose, PLGA microspheres will be used as carrier for the local release of resolvin E1 during PD. To prove our concept that arthritis can be suppressed by treatment of PD, rice rats with chronic PD and induced arthritis will be treated with a periodontal treatment delivery system containing RvE1. The severity of chronic arthritis and periodontitis will be scored clinically, radiological, histopathological, immunological (markers of inflammation and autoreactivity) and microbiological.