SAT0677 Prevotella Copri in Individuals at Risk for Rheumatoid Arthritis

Background Prevotella spp. have been identified as highly enriched in the intestinal microbiota of patients newly diagnosed with rheumatoid arthritis (RA), suggesting a role in the development of the disease.1 Sequence homology between RA-specific autoantigens and proteins of Prevotella copri have been reported.2 However, the role of these bacteriae in the pathogenesis of the disease is not yet established. Objectives To determine the microbiome composition and prevalence of Prevotella spp. in different pre-clinical phases of RA, in a group of individuals at risk for RA, namely first degree relatives of patients with RA (RA-FDR). Methods In an ongoing cohort study of RA-FDR, enrolling individuals without clinical evidence of RA at inclusion, we categorised individuals in the following groups: ‘healthy controls’: asymptomatic RA-FDR without any autoantibodies or symptoms associated with possible RA; ‘pre-clinical RA’: individuals with ‘systemic autoimmunity associated with RA’ defined by the presence of anti-citrullinated peptide antibodies (ACPA) or rheumatoid factor (RF) and/or symptomatic individuals with clinically suspect arthralgias or unclassified arthritis. Participants provided stool samples for microbiome analysis. We excluded subjects who had undergone antibiotic therapy within the last 3 months, with known history of inflammatory bowel disease and/or gastrointestinal tract surgery ever. Stool samples processing and microbial diversity culture-independent analyses were performed. After DNA extraction, the V4 region of the 16S rRNA gene was amplified using barcoded primers and sequencing was done on an Illumina MiSeq. Statistical analyses of community structures were performed.3 Results Of the 134 participants enrolled, 51 were categorised as ‘healthy controls’ and 83 as ‘pre-clinical RA’. table 1 shows the general characteristics of the two groups. The microbiota of ‘pre-clinical RA’ individuals was significantly altered compared to ‘healthy controls’, with abundance of specific bacteria, particularly an enrichment of Prevotella spp. (figure 1).Abstract SAT0677 – Table 1 General characteristics of participants Characteristics Healthy controls n=51 Pre-clinical RA** n=83 Age, median (IQR) 55 (47–62) 58 (50–66) Female sex, n (%) 39 (76) 74 (89) Current Smoking, n (%) 12 (23) 16 (19) Current Alcohol, n (%) 22 (46) 29(41 Body mass index, median(IQR) 24 (22–27) 24 (22–27) Obesity, BMI≥30, n (%) 5 (10) 9 (11) ACPA positivity, n (%) 0 (0) 38 (46)* RF positivity, n (%) 0 (0) 28 (34)* Shared epitope (1 or 2 copies), n (%) 32 (65) 42 (52) *p-value<0.05, Kruskal-Wallis test for continuous variables and Fisher’s exact test for categorical variables. **Pre-clinical RA group includes individuals with ACPA or RF positivity and/or with arthralgia or unclassified arthritis.Abstract SAT0677 – Figure 1 Linear discriminant analysis (LDA) effect size (LEfSe) estimates the different relative abundance of bacteria in Healthy controls and Pre-clinical RA participants Conclusions Individuals at risk of RA who have developed systemic autoimmunity associated with RA and/or symptoms, have enrichment of Prevotella spp in comparison with healthy controls. Our findings support the hypothesis of a causal role of Prevotella spp in the development of RA, which could lead to future attempts to interfere with its intestinal colonisation during the preclinical stages of disease. References [1] Scher JU, et al. eLife2013;2:e01202. [2] Pianta A, et al. J Clin Invest2017;127(8):2946–56. [3] Segata N, et al. Genome Biology2011;12:R60. Disclosure of Interest None declared