Oral Metagenomic Biomarkers in Rheumatoid Arthritis
Abstract
Rheumatoid arthritis (RA) affects ~2 million in the United States. The Department of Veterans Affairs (VA) health system provides care for more than 100,000 RA patients based on claims data and diagnostic code usage. RA is an autoimmune disease that is associated with frequent disability and increased mortality. Work-related disability from RA is among the highest of all common diseases, affecting from 30% to 60% of patients. Mortality rate among US male Veterans with RA is more than twice that expected in an age-matched population. RA is also increasingly recognized to be associated with higher risk of cardiovascular disease, resulting in significant impact to the individual and to society. Treatment for RA focuses on controlling symptoms and preventing joint damage. The cause of RA remains unknown. Genetics play a role in RA, but genetics alone are not sufficient to explain the development of RA since in only 25% of cases do both individuals from a pair of identical twins suffer from RA. This suggests that there are other environmental triggers for the disease. Our working hypothesis is that RA, like certain other autoimmune diseases, is caused by the presence of certain disease-causing bacteria. The association of RA and periodontal disease has been identified and reported for many years. Since periodontal disease is clearly caused by a certain subset of bacteria in the oral cavity, it is reasonable to consider that some oral bacteria may be the missing link, playing a causative role in RA. In spite of recent interests in bacterial contributions to RA, there has not been a systematic evaluation of oral bacteria in this disease. Our study is a multidisciplinary proposal with five investigators from different, yet complementary, disciplines to initiate this new discovery type project. This project is based on the collaboration of a rheumatologist, a dentist, oral biologists, and infectious disease experts with expertise in immunology, microbiology, and genomics. In brief, RA patients will be recruited by the rheumatologist, who is primarily responsible for the RA clinic at our university and at a neighboring VA medical center. A total of 100 participants will be recruited for two groups of patients/controls. Group 1 will be 25 RA adult patients who have not been treated with biologics (considered "early" or milder form of RA) to be compared to 25 paired healthy controls from age-matched member of the same household. Group 2 will be 25 RA patients who are responsive to first line anti-TNF therapy (RA patients with severe disease needing treatment with biologics) versus 25 age/sex-matched RA patients who are resistant to two or more TNF antagonists (RA patients who are not responsive to treatment with biologics). Selected RA patients and controls will be scheduled to be seen by our experienced dental faculty collaborator in this project for the collection of dental plaques, which will be sent to our genomic sequencing expert collaborator to perform deep sequencing analyses. The comparison of results from Group 1 will tell us whether there are unique bacteria more abundant in RA patients compared to controls. The comparison of results from Group 2 will tell us whether there are differences in bacteria between RA patients who are responsive or non-responsive to biologics. The deep sequencing data will allow us to go beyond naming the bacteria strains that are different but also subspecies that may play an important role in the disease process. The current concept is that a given bacteria may have different substrains; some substrains may not cause disease while other substrains will cause disease. By obtaining a large amount of sequencing data (deep sequencing), we will be able to identify the disease-causing substrains associated with different stages of RA. If we are successful in identifying disease-associated bacterial biomarkers for RA, this could open a new area of research into the true
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510320
Entities
People
- Edward Chan
Organizations
- United States Army
- University of Florida