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Abstract

Background The response to TNF-blockers in axial spondyloarthritis (AxSpA) is at least partially influenced by HLA-B27 through a still poorly understood mechanism.Objectives Given that HLA-B27 regulates the gut microbiota composition in rats1,2, we seek to evaluate the predictive value of the gut microbiota composition in AxSpA patients on their responsiveness to TNF-blockers.Methods A total of 58 patients was monocentrically recruited between October 2014 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 (̑extpm}SD) was 45.6{̑extpm}21.4; ASDAS 2.8{̑extpm}0.9 and CRP 9.7{̑extpm11.4 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.Results 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 report3, the abundance of Ruminococcus gnavus 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 Clostridiales order was associated with a better response to the treatment and with the HLA-B27 genotype.Conclusions 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.References [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.Disclosure of Interest None declared