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Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients

We previously found that leflunomide combined with low-dose prednisone rapidly improved the clinical symptoms of myasthenia gravis (MG), but we had not investigated the mechanism of this phenomenon. This study documents the effect of leflunomide combined with low-dose prednisone on pro-inflammatory...

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Autores principales: Huang, Xin, Ran, Hao, Li, Yingkai, Ma, Qian, Ou, Changyi, Qiu, Li, Feng, Huiyu, Liu, Weibin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508276/
https://www.ncbi.nlm.nih.gov/pubmed/36164461
http://dx.doi.org/10.3389/fneur.2022.961628
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author Huang, Xin
Ran, Hao
Li, Yingkai
Ma, Qian
Ou, Changyi
Qiu, Li
Feng, Huiyu
Liu, Weibin
author_facet Huang, Xin
Ran, Hao
Li, Yingkai
Ma, Qian
Ou, Changyi
Qiu, Li
Feng, Huiyu
Liu, Weibin
author_sort Huang, Xin
collection PubMed
description We previously found that leflunomide combined with low-dose prednisone rapidly improved the clinical symptoms of myasthenia gravis (MG), but we had not investigated the mechanism of this phenomenon. This study documents the effect of leflunomide combined with low-dose prednisone on pro-inflammatory T cells in MG patients. We compared 32 treated MG patients with 18 controls. We collected peripheral blood before treatment and 4, 8, and 12 weeks after treatment. We extracted peripheral blood mononuclear cells (PBMCs) and stimulated them with phorbol 12-myristate 13-acetate (PMA) + ionomycin and quantified IFN-γ, IL-4, IL-17, and IL-9 secretion through ELISA. We quantified T helper (Th) cells Th1 (CD3+CD4+IFN-γ+), Th2 (CD3+CD4+IL-4+), Th17 (CD3+CD4+IL-17A+) and Th9 (CD3+CD4+IL-9+) among PBMCs. The treatment significantly reduced IL-17 and IL-9 secretion in peripheral blood but did not affect IFN-γ levels. Significant decreases in IL-17 and IL-9 appeared at week 12, and the trend of change was similar to that of the MG composite score. Flow cytometry indicated that leflunomide combined with low-dose prednisone significantly reduced the frequency of Th1 and Th17 cells. These findings demonstrate the potential of this treatment as an alternative immunosuppressive therapy for MG.
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spelling pubmed-95082762022-09-25 Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients Huang, Xin Ran, Hao Li, Yingkai Ma, Qian Ou, Changyi Qiu, Li Feng, Huiyu Liu, Weibin Front Neurol Neurology We previously found that leflunomide combined with low-dose prednisone rapidly improved the clinical symptoms of myasthenia gravis (MG), but we had not investigated the mechanism of this phenomenon. This study documents the effect of leflunomide combined with low-dose prednisone on pro-inflammatory T cells in MG patients. We compared 32 treated MG patients with 18 controls. We collected peripheral blood before treatment and 4, 8, and 12 weeks after treatment. We extracted peripheral blood mononuclear cells (PBMCs) and stimulated them with phorbol 12-myristate 13-acetate (PMA) + ionomycin and quantified IFN-γ, IL-4, IL-17, and IL-9 secretion through ELISA. We quantified T helper (Th) cells Th1 (CD3+CD4+IFN-γ+), Th2 (CD3+CD4+IL-4+), Th17 (CD3+CD4+IL-17A+) and Th9 (CD3+CD4+IL-9+) among PBMCs. The treatment significantly reduced IL-17 and IL-9 secretion in peripheral blood but did not affect IFN-γ levels. Significant decreases in IL-17 and IL-9 appeared at week 12, and the trend of change was similar to that of the MG composite score. Flow cytometry indicated that leflunomide combined with low-dose prednisone significantly reduced the frequency of Th1 and Th17 cells. These findings demonstrate the potential of this treatment as an alternative immunosuppressive therapy for MG. Frontiers Media S.A. 2022-09-09 /pmc/articles/PMC9508276/ /pubmed/36164461 http://dx.doi.org/10.3389/fneur.2022.961628 Text en Copyright © 2022 Huang, Ran, Li, Ma, Ou, Qiu, Feng and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Huang, Xin
Ran, Hao
Li, Yingkai
Ma, Qian
Ou, Changyi
Qiu, Li
Feng, Huiyu
Liu, Weibin
Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients
title Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients
title_full Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients
title_fullStr Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients
title_full_unstemmed Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients
title_short Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients
title_sort leflunomide combined with low-dose prednisone inhibits proinflammatory t cells responses in myasthenia gravis patients
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508276/
https://www.ncbi.nlm.nih.gov/pubmed/36164461
http://dx.doi.org/10.3389/fneur.2022.961628
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