TY - JOUR T1 - Polyfunctional IL-17A+ MAIT cells are expanded in the peripheral blood of patients with HLA-B27+ axial spondyloarthritis JF - bioRxiv DO - 10.1101/2022.01.17.475829 SP - 2022.01.17.475829 AU - Micah Lefton AU - Nihaarika Sharma AU - Akash R. Patel AU - Jeffrey A. Sparks AU - Joerg Ermann Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/01/18/2022.01.17.475829.abstract N2 - Objectives Studies in axial spondyloarthritis (axSpA) have yielded conflicting results regarding the identity of the major IL-17A-producing lymphocyte populations. The goal of this study was to comprehensively assess the production of IL-17A and related cytokines by peripheral blood lymphocytes in axSpA.Methods Peripheral blood mononuclear cells were isolated from patients with axSpA and healthy controls matched for age, sex and HLA-B27 status. Unstimulated cells and cells activated with PMA/Ionomycin were analyzed by 25-parameter fluorescent flow cytometry. Data were analyzed by hierarchical gating, UMAP and SPICE.Results Except for a reduced frequency of mucosal-associated invariant T (MAIT) cells and natural killer (NK) cells, there were no other significant differences in abundance of major lymphocyte populations in axSpA patients compared with controls. Increased IL-17A production in axSpA was observed in total non-B lymphocytes and in MAIT cells. The fraction of MAIT cells expressing the tissue residency markers CD69 and CD103 was increased in axSpA. CD103 positive MAIT cells were enriched for IL-17A producers. axSpA patients demonstrated an expansion of MAIT cell subsets producing IL-17A, IL-17F, GM-CSF and TNF. This expansion was only observed in HLA-B27+ patients.Conclusions We document an expansion of polyfunctional IL-17A+ MAIT cells in the peripheral blood of HLA-B27+ patients with axSpA. These results are consistent with the implied role of intestinal dysbiosis or inflammation in axSpA pathogenesis.Key messages What is already known about this subject? Various IL-17A-producing lymphocyte populations have been implicated in the pathogenesis of axSpA.What does this study add? Polyfunctional MAIT cells capable of producing IL-17A, IL-17F, GM-CSF and TNF are expanded in the peripheral blood of HLA-B27+ patients with axSpA.How might this impact on clinical practice or future developments? Overproduction of IL-17A by MAIT cells is the most consistent finding of peripheral blood lymphocyte studies in axSpA.Our data support the pathogenetic link between intestinal and axial inflammation in axSpA.Competing Interest StatementThe authors have declared no competing interest. ER -