Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Characteristic Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA): A Trigger for Autoimmunity?
Scher7, Jose U., Ubeda3, Carles, Pillinger2, Michael H., Bretz6, Walter, Buischi6, Yvonne, Rosenthal7, Pamela B., Reddy7, Soumya M.
Lucille Castori Center for Microbes, Inflammation, and Cancer/MSKCC
NYU School of Medicine, NYU Hospital for Joint Diseases, New York, NY
Manhattan VA Med Hospital, New York, NY
Memorial Sloan-Kettering Cancer Center (MSKCC)
New York University Hospital for Joint Disease, New York, NY
New York University Medical Center, New York, NY
NYU College of Dentistry
NYU Hospital for Joint Diseases, New York, NY
NYU Hospital for Joint Diseases
NYU School of Medicine
The etiology of RA remains unknown, but genetic and environmental factors have been implicated. An infectious trigger has been sought but conventional microbiologic techniques have been uninformative. The human intestine contains a dense, diverse and poorly characterized (>=80% uncultured) bacterial population whose collective genome (microbiome) is >=100 times larger than its human host. We (DRL) have recently shown in mice that gut-residing bacteria drive autoimmune arthritis via Th17 cell activation (Immunity 2010). Multiple lines of investigation also suggest a link between RA and oral microbes.
As part of an NIH ARRA grant, the NYU Microbiome Center for Rheumatology and Autoimmunity was established to study gut and oral microbiota in RA and related conditions. A cross-sectional study and prospective proof-of-concept antibiotic intervention trial are ongoing. Fecal samples are collected, periodontal status assessed and oral samples obtained by subgingival biofilm collection. To date, oral/intestinal microbiomes have been analyzed in 8 RA patients, 3 psoriatic arthritis (PsA) patients and 9 healthy controls. Periodontal status was characterized in 30 RA, 4 PsA and 8 controls. DNA was purified and variable 16s rRNA gene regions amplified. PCR products were pyrosequenced (454 Life Sciences), and DNA sequences compared to the RDP and BLAST catalogs. rDNA-based phylogenetic trees were created, and the UNIFRAC metric used to compare bacterial communities across individuals. Sera from all subjects were evaluated for anti-citrullinated peptide antibodies (ACPA).
Prevotellaceae family was significantly overrepresented in fecal microbiota from ACPA+ RA patients (range 13%-85%; mean=38%) vs ACPA- individuals (mean=4.3%); p=0.003. One ACPA+ healthy individual and 1 ACPA+ PsA patient shared similar microbiomes with ACPA+ RA. Subgingival microbiomes in patients with new-onset drug-naive RA exhibited overabundance of the Spirochetaceae/Prevotellaceae/Porphyromonaceae families (mean=53%) compared to chronic-active RA and healthy controls (mean=18.5%). Periodontal assessment revealed 78% of examined sites bled upon probing in RA patients (mean age 39; 73% female), significantly more than controls (38% PsA, 12% healthy; p<0.001 vs RA); 66% of RA patients also presented with moderate periodontitis compared to PsA (25%) and controls (12%).
This is the first study using high-throughput technologies to assess oral and intestinal microbiota in RA. Our data corroborate prior reports demonstrating an underappreciated high prevalence of periodontal disease at a young age in patients with RA. Moreover, our preliminary data suggest that ACPA generation may be associated with larger populations of Prevotellaceae in both oral and intestinal microbiomes. In response to such altered microbial flora, certain predisposed individuals may develop auto-inflammatory disease, through mechanisms that may include the generation of cyclic citrullinated peptides or Th17 cell activation in the intestinal mucosa. Thus, the oral and intestinal microbiota merit further investigation as potential triggers for autoimmunity and clinical RA.
To cite this abstract, please use the following information:
Scher, Jose U., Ubeda, Carles, Pillinger, Michael H., Bretz, Walter, Buischi, Yvonne, Rosenthal, Pamela B., et al; Characteristic Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA): A Trigger for Autoimmunity? [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1390