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Immune Skew of Circulating Follicular Helper T Cells Associates With Myasthenia Gravis Severity

OBJECTIVE: To clarify functional alterations of follicular helper T cells (Tfh) in myasthenia gravis (MG) because Tfh play important roles in helping B cells generate antibody-producing cells. METHODS: A total of 24 immunotherapy-naive patients with anti–acetylcholine receptor (AchR) antibody–positi...

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Autores principales: Ashida, Shinji, Ochi, Hirofumi, Hamatani, Mio, Fujii, Chihiro, Kimura, Kimitoshi, Okada, Yoichiro, Hashi, Yuichiro, Kawamura, Kazuyuki, Ueno, Hideki, Takahashi, Ryosuke, Mizuno, Toshiki, Kondo, Takayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105905/
https://www.ncbi.nlm.nih.gov/pubmed/33436376
http://dx.doi.org/10.1212/NXI.0000000000000945
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author Ashida, Shinji
Ochi, Hirofumi
Hamatani, Mio
Fujii, Chihiro
Kimura, Kimitoshi
Okada, Yoichiro
Hashi, Yuichiro
Kawamura, Kazuyuki
Ueno, Hideki
Takahashi, Ryosuke
Mizuno, Toshiki
Kondo, Takayuki
author_facet Ashida, Shinji
Ochi, Hirofumi
Hamatani, Mio
Fujii, Chihiro
Kimura, Kimitoshi
Okada, Yoichiro
Hashi, Yuichiro
Kawamura, Kazuyuki
Ueno, Hideki
Takahashi, Ryosuke
Mizuno, Toshiki
Kondo, Takayuki
author_sort Ashida, Shinji
collection PubMed
description OBJECTIVE: To clarify functional alterations of follicular helper T cells (Tfh) in myasthenia gravis (MG) because Tfh play important roles in helping B cells generate antibody-producing cells. METHODS: A total of 24 immunotherapy-naive patients with anti–acetylcholine receptor (AchR) antibody–positive MG and 18 age-matched healthy subjects (HS) were enrolled. Samples from 6 patients were available for posttreatment analysis. Subsets of circulating Tfh (cTfh) and B cells were identified by flow cytometry analysis of surface molecules. Cytokine production by isolated cTfh subsets from 5 patients with MG and 5 HS was measured in vitro. Analysis was performed to examine the correlation between the frequency of cTfh subsets and that of plasmablasts and between cTfh subsets and the quantitative MG score. RESULTS: cTfh increased with elevated expression of inducible T-cell costimulator (ICOS) in patients with MG. cTfh shifted to Th2 and Th17 over Th1 in MG. ICOS(high)cTfh produced significantly higher levels of interleukin (IL)-21, IL-4, and IL-17A than ICOS(low) cTfh only in patients with MG. The frequency of cTfh within CD4 T cells was more closely associated with disease severity than the serum anti-AchR antibody titer and frequency of plasmablasts within B cells. Abnormalities of cTfh were improved after immunotherapy in parallel with clinical improvement. CONCLUSIONS: Alternation of cTfh is a key feature in the development of MG and may become a biomarker for disease severity and therapeutic efficacy. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the level of cTfh is associated with disease severity in patients with MG.
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spelling pubmed-81059052021-05-10 Immune Skew of Circulating Follicular Helper T Cells Associates With Myasthenia Gravis Severity Ashida, Shinji Ochi, Hirofumi Hamatani, Mio Fujii, Chihiro Kimura, Kimitoshi Okada, Yoichiro Hashi, Yuichiro Kawamura, Kazuyuki Ueno, Hideki Takahashi, Ryosuke Mizuno, Toshiki Kondo, Takayuki Neurol Neuroimmunol Neuroinflamm Article OBJECTIVE: To clarify functional alterations of follicular helper T cells (Tfh) in myasthenia gravis (MG) because Tfh play important roles in helping B cells generate antibody-producing cells. METHODS: A total of 24 immunotherapy-naive patients with anti–acetylcholine receptor (AchR) antibody–positive MG and 18 age-matched healthy subjects (HS) were enrolled. Samples from 6 patients were available for posttreatment analysis. Subsets of circulating Tfh (cTfh) and B cells were identified by flow cytometry analysis of surface molecules. Cytokine production by isolated cTfh subsets from 5 patients with MG and 5 HS was measured in vitro. Analysis was performed to examine the correlation between the frequency of cTfh subsets and that of plasmablasts and between cTfh subsets and the quantitative MG score. RESULTS: cTfh increased with elevated expression of inducible T-cell costimulator (ICOS) in patients with MG. cTfh shifted to Th2 and Th17 over Th1 in MG. ICOS(high)cTfh produced significantly higher levels of interleukin (IL)-21, IL-4, and IL-17A than ICOS(low) cTfh only in patients with MG. The frequency of cTfh within CD4 T cells was more closely associated with disease severity than the serum anti-AchR antibody titer and frequency of plasmablasts within B cells. Abnormalities of cTfh were improved after immunotherapy in parallel with clinical improvement. CONCLUSIONS: Alternation of cTfh is a key feature in the development of MG and may become a biomarker for disease severity and therapeutic efficacy. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the level of cTfh is associated with disease severity in patients with MG. Lippincott Williams & Wilkins 2021-01-12 /pmc/articles/PMC8105905/ /pubmed/33436376 http://dx.doi.org/10.1212/NXI.0000000000000945 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Ashida, Shinji
Ochi, Hirofumi
Hamatani, Mio
Fujii, Chihiro
Kimura, Kimitoshi
Okada, Yoichiro
Hashi, Yuichiro
Kawamura, Kazuyuki
Ueno, Hideki
Takahashi, Ryosuke
Mizuno, Toshiki
Kondo, Takayuki
Immune Skew of Circulating Follicular Helper T Cells Associates With Myasthenia Gravis Severity
title Immune Skew of Circulating Follicular Helper T Cells Associates With Myasthenia Gravis Severity
title_full Immune Skew of Circulating Follicular Helper T Cells Associates With Myasthenia Gravis Severity
title_fullStr Immune Skew of Circulating Follicular Helper T Cells Associates With Myasthenia Gravis Severity
title_full_unstemmed Immune Skew of Circulating Follicular Helper T Cells Associates With Myasthenia Gravis Severity
title_short Immune Skew of Circulating Follicular Helper T Cells Associates With Myasthenia Gravis Severity
title_sort immune skew of circulating follicular helper t cells associates with myasthenia gravis severity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105905/
https://www.ncbi.nlm.nih.gov/pubmed/33436376
http://dx.doi.org/10.1212/NXI.0000000000000945
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