Oral Metagenomic Biomarkers in Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Observational

Summary: 
      Rheumatoid Arthritis (RA) is a chronic and potentially severe autoimmune disease affecting 2
      million in the United States. The role of environmental factors in modulating autoimmunity
      pathogenesis has been clearly described and yet the specific mechanisms of action remain
      poorly understood. A growing body of evidence implicates microbiota of mucosal surfaces in
      the development of autoimmune disorders. Various studies have clearly linked RA to
      periodontal disease. The latter is linked to the red-complex that includes the oral bacterium
      Porphyromonas gingivalis. And yet there has not been a systematic analysis of the oral
      microbiota in RA to determine whether there are specific markers for P. gingivalis (and other
      oral bacteria) that are linked to RA.

      In this study, the investigators will characterize oral microbial composition (microbiome)
      and gene content (metagenome) of DNA isolated from oral samples obtained from patients with
      (i) early stage RA prior to biologics treatments and (ii) subsets of RA patients who are
      responsive or unresponsive to anti-TNF-alpha therapy. The innovative aspect of this study is
      going beyond the identification of oral bacterial species, to the level of strains and genes
      that are associated with these groups. The overall hypothesis is that oral microbial
      variation exists between individuals that influences development of autoimmunity and
      autoimmune disease.
    

Detailed description: 
      This is a multi-disciplinary research study with five investigators from different, yet
      complementary, disciplines to establish this new collaboration. There is a high translational
      potential for information gained from this project 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 participants will be recruited by the
      rheumatologist. A total of 100 participants will be recruited for two groups to be studied;
      one group of subjects with RA and the other group will be healthy controls. These two groups
      will be divided into the following groups for participation in the study: Group 1: will
      consist of 25 RA adult subjects who have not been treated with biologics which will be
      compared to 25 healthy controls from age-matched members of the same household. Group 2 will
      consist of 25 RA adult subjects responsive to first line anti-TNF therapy which will be
      compared to 25 subjects of the same age and sex with RA who are resistant to two or more TNF
      antagonists. The participants will be scheduled for a research study visit at the University
      of Florida Dental Clinic Research Unit. During the exam the following will take place: the
      multidimensional health assessment questionnaire (MDHAQ), dental exam, saliva collection, and
      dental plaque will be removed from different tooth surfaces for supragingival.

      The supragingival will be subjected to deep sequencing in the genomics lab. To test two
      specific aims: 1) testing the hypothesis that oral microbiome profiles based on 16S RNA data
      are associated with the development of RA or with the response to a specific therapy, and 2)
      testing the hypothesis that the specific genes, variants, and functional capabilities
      (metagenome) are associated with RA or with therapeutic response. Upon completion of this
      pilot study, the investigators will have systematically identified bacterial biomarkers (e.g.
      species, subspecies, genes) that correlate with RA and may serve as potential targets for
      disease treatment. These markers may be developed into new drug targets for RA therapy in
      future studies.
    

Intervention name(s): Dental Plaque; Multi-dimensional health assessment questionnaire (MDHAQ); Saliva Collection
Intervention type(s): Procedure; Other; Other
Intervention description(s): All participants will have dental plaque removed from different tooth surfaces for supragingival.; The RA groups will receive the multi-dimensional health assessment questionnaire (MDHAQ) for physical function, pain, and global status.; All participants will have a saliva collection.
Other intervention name(s): MDHAQ
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Rheumatoid Arthritis (RA) adult patients who have not been treated with biologics (naïve to
        biologics), RA patients responsive to first line anti-TNF therapy, RA patients who are
        resistant to two or more TNF antagonists, and healthy controls from age-matched members of
        the same household.
      
Biospecimen description: 
      Supragingival dental plaque will be pooled from different tooth surfaces using sterile
      periodontal curettes. DNA samples will be subjected to deep sequencing.
    
Keywords: Rheumatoid arthritis; Metagenome; microbiome