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Exploring frequencies of circulating specific Th17 cells against myeloperoxidase and proteinase 3 in ANCA associated vasculitis Martinez Valenzuela, Laura Draibe, Juliana Quero Ramos, Maria Fulladosa, Xavier Cruzado, Josep Ma. Bestard Matamoros, Oriol Torras Ambròs, Joan Vasculitis Diagnòstic Cèl·lules Immunologia Vasculitis Diagnosis Cells Immunology Background: the role of the T helper 17 (Th17) cell subset in anti-neutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV) is controversial. We hypothesized that a specific Th17 response to myeloperoxidase (MPO) or proteinase 3 (PR3) is detectable in AAV patients and is different among the disease phases. Methods: we analyzed 43 AAV patients with renal involvement (21 acute and 22 remission patients), and 12 healthy controls. Peripheral blood mononuclear cells (PBMCs) were cultured with PR3/MPO over 48 h. Thereafter, frequencies of MPO/PR3-specific Th17 cells were assessed using an enzyme-linked immunosorbent spot (ELISpot) assay. Supernatant IL-17 concentration was quantified using ELISA. Finally, specific Th17 response after depletion of T regulatory lymphocytes (T-regs) in some remission patients was compared to the non T-reg-depleted response. Results: specific Th17 cell number was higher in acute patients compared to remission (p = 0.004). Specific Th17 cell number performed well in the disease activity detection (ROC curve area under the curve (AUC) = 0.87; p = 0.0001) with an optimal cut-off of 6 spots/million. Patients above this cut-off showed higher serum creatinine (p = 0.004), C-reactive protein (CRP) (p = 0.001) and ANCA titer (p = 0.032). Supernatant IL-17 concentration was higher in acute patients compared to remission (p = 0.035) and did not normalize to healthy control levels (p = 0.01). Conclusions: a specific Th17 cell response is present in AAV patients. This response is more pronounced in the acute phase, but persists in remission. 2020-07-09T11:07:56Z 2020-07-09T11:07:56Z 2019-11-20 2020-07-09T11:07:57Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.3390/ijms20235820 International Journal of Molecular Sciences, 2019, vol. 20, num. 23, p. 5820 https://doi.org/10.3390/ijms20235820 cc-by (c) Martínez Valenzuela, Laura et al., 2019 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess MDPI Articles publicats en revistes (Ciències Clíniques)