SAT0265 The response to tnf-blockers treatment of spa patients is influenced by the interplay between hla-b27 and gut microbiota composition at baseline
Authors: M. Vallier, M. Chamaillard, S. Ferreira, S. Menegatti, E. Bianchi, L. Rogge, M. Dougados, C. Miceli-Richard
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The response to TNF-blockers in axial spondyloarthritis (AxSpA) is at least partially influenced by HLA-B27 through a still poorly understood mechanism. <h3>Objectives</h3> Given that HLA-B27 regulates the gut microbiota composition in rats<sup>1,2</sup>, we seek to evaluate the predictive value of the gut microbiota composition in AxSpA patients on their responsiveness to TNF-blockers. <h3>Methods</h3> A total of 58 patients was monocentrically recruited between <sup>October 2014</sup> and May 2015. At baseline, these patients had an active disease despite NSAIDs intake and were eligible for treatment with a TNF-blocker, while having no history of inflammatory bowel disease (IBD). The mean BASDAI (±SD) was 45.6±21.4; ASDAS 2.8±0.9 and CRP 9.7±11.4 mg/L. Among these patients, 56 fulfilled the ASAS classification criteria (imaging arm) with sacro-iliitis on X-rays (n=37) or objective signs of inflammation on MRI (n=48). Two patients fulfilled the clinical arm. These patients were not subjected to antibiotics within 3 months before stool sample collection. Bacterial 16S rRNA gene sequencing of the V3-V4 region was performed on stools samples before and 3 months after TNF-blocker treatment. Beta diversity metrics were calculated on the abundance of operational taxonomic units (OTU) after their taxonomic assignment on quality-filtered sequences. <h3>Results</h3> Principal component analysis (PCA) ordination of Bray-Curtis similarity revealed that current smoking (compared with never or ever smokers) and HLA-B27 genotype were significantly associated with the overall composition of the microbiota at baseline. Meanwhile, the abundance of eleven bacterial OTUs was influenced by HLA-B27 genotype at baseline but not after 3 month of treatment. In contrast, we identified a bacterial signature that was linked to the smoking behaviour independently of TNF-blocker treatment, whereas the BASDAI and ASDAS indices were significantly associated to the general composition of the gut microbiota after the 3 month treatment. In line with a previous report<sup>3</sup>, the abundance of <i>Ruminococcus gnavus</i> was not associated with disease activity in the absence of IBD. Interestingly, the abundance of 5 and 7 bacterial OTUs at baseline was associated with the response to TNF-blockers assessed by BASDAI and ASDAS, respectively. Among these candidates, the abundance of one bacterial OTUs belonging to the <i>Clostridiales</i> order was associated with a better response to the treatment and with the HLA-B27 genotype. <h3>Conclusions</h3> Anti-TNF treatment was found to modulate the HLA-B27-induced variations of the intestinal microbiota of AxSpA patients. Moreover, the abundance of a subset of OTUs at baseline was found to predict the responsiveness to TNF-blockers. Further functional studies will be conducted to assess how these taxa can be use as predictors of the treatment outcome. <h3>References</h3> [1] Gill, et al. Effects of HLA-B27 on Gut Microbiota in Experimental Spondyloarthritis Implicate an Ecological Model of Dysbiosis. Arthritis Rheumatol2017. [2] Lin, et al. HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats. PLoS One2014. [3] Breban, et al. Faecal microbiota study reveals specific dysbiosis in spondyloarthritis.Annal Rheum Dis2017. <h3>Disclosure of Interest</h3> None declared