FRI0361 INNATE VERSUSADAPTIVE IL-17A PRODUCING CELLS IN AXIAL SPONDYLOARTHRITIS

Background IL-17A-inhibition has been very successful in AxSpA but the cell populations targeted by this new therapeutic remain unknown. This question is relevant because the recent failure of anti-IL-23 in AxSpA demonstrated that IL-23-independent IL-17-producing cells may be of particular relevance for SpA pathogenesis. Some data from literature suggests the involvement of MAIT, γδ T, and neutrophils as IL-17A producing cells in AxSpA (1–3). However, even though they may be responsible for IL-17A-mediated inflammation, it is still unclear which is the major IL-17A-producing cell population in this disease. Objectives To assess and compare gene expression profiles of neutrophils, MAIT, γδ, CD4+ and CD8+ T cells from AxSpA patients. Methods We recruited 5 healthy donors and 10 patients with a diagnosis of AxSpA according to the ASAS criteria. We compared the gene expression profiles of 5 sorted cell populations: 3 innate cell populations (neutrophils, MAIT and γδ T cells) and 2 adaptive cell populations (CD4+T and CD8+T) after cell stimulation by PMA + A23187 (calcium ionophore) + β1,3 glucan (extracted from Aspergillus fumigatus hyphae). Published data suggested that neutrophils stimulation by Aspergillus fumigatus induces IL-17A production by these cells(4). For each of these cell populations, cytokine production and the expression of a panel of 755 genes (Autoimmune discovery panel from Nanostring including 43 genes for which a polymorphism was associated with AS) were assessed. Patient and control groups were compared with a Mann-Whitney test and comparison of cell populations was performed by a multigroup comparison. Results There was no significant difference between patients and controls regarding gene expression profile of neutrophils, γδ T, CD4+T and CD8+T. We observed that 34 genes were differentially expressed between patients and controls in MAIT cells (p = 0.03, q = 0.1). In particular, T cell activation genes (TBX21, AHR, ZAP70) and cell interaction genes (ITAG6, CTNNB1, ICAM2, ITGB2, SELL) were decreased in patients. Among AxSpA patients, MAIT cells were those significantly showing the highest level of IL-17A expression. IL23R and RORC were also more expressed by MAIT compared to others cell populations. IL-17A expression was very low in neutrophils but we observed that 18 out of the 43 AS associated genes were mainly expressed by neutrophils (p Conclusion These preliminary data confirm that the innate immune cells could play an important role in AxSpA. MAIT cells are at the forefront of the expression of IL-17A before γδ T, CD4+T and CD8+T. Neutrophils do not appear to participate in the production of IL-17A, but the high expression of AS linked genes in these cells suggests their involvement in AxSpA. References [1] Appel H, et al. Analysis of IL-17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response. Arthritis Res Ther. 2011 [2] Kenna TJ, et al. Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive γ/δ T cells in patients with active ankylosing spondylitis. Arthritis Rheum. 2012 [3] Gracey E, et al. IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis. Ann Rheum Dis. 2016 [4] Taylor PR, et al. Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγt and dectin-2. Nat Immunol. 2014 Disclosure of Interests nicolas rosine: None declared, Surya Koturan: None declared, Hanane Yahia: None declared, Claire Leloup: None declared, Elisabetta Bianchi: None declared, Corinne Miceli Richard Grant/research support from: MSD, Pfizer, AbbVie, Biogen, UCB, Novartis, Consultant for: Abbvie, Novartis, BMS, Lars Rogge: None declared