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The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and Restored by Rituximab

Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe auto-immune disease of the central nervous system driven by pathogenic antibodies mainly directed against aquaporin-4 (AQP4-Ab). Treatment of NMOSD currently relies on immunosuppressants (mycophenolate mofetil, azathioprine) or B-ce...

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Autores principales: Nicolas, Philippe, Ruiz, Anne, Cobo-Calvo, Alvaro, Fiard, Guillaume, Giraudon, Pascale, Vukusic, Sandra, Marignier, Romain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877601/
https://www.ncbi.nlm.nih.gov/pubmed/31803192
http://dx.doi.org/10.3389/fimmu.2019.02686
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author Nicolas, Philippe
Ruiz, Anne
Cobo-Calvo, Alvaro
Fiard, Guillaume
Giraudon, Pascale
Vukusic, Sandra
Marignier, Romain
author_facet Nicolas, Philippe
Ruiz, Anne
Cobo-Calvo, Alvaro
Fiard, Guillaume
Giraudon, Pascale
Vukusic, Sandra
Marignier, Romain
author_sort Nicolas, Philippe
collection PubMed
description Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe auto-immune disease of the central nervous system driven by pathogenic antibodies mainly directed against aquaporin-4 (AQP4-Ab). Treatment of NMOSD currently relies on immunosuppressants (mycophenolate mofetil, azathioprine) or B-cell-depleting therapy (rituximab). B-cell differentiation into antibody-producing cells requires T follicular helper cells (Tfh). There are several Tfh subsets that differentially affect B-cell differentiation; Tfh2 and Tfh17 subsets strongly support B-cell differentiation. By contrast, Tfh1 lack this capacity and T follicular regulatory cells (Tfr), inhibit B-cell differentiation into antibody-producing cells. We performed a broad characterization of circulating Tfh subsets in 25 NMOSD patients and analyzed the impact of different treatments on these subsets. Untreated NMOSD patients presented a Tfh polarization toward excessive B-helper Tfh subsets with an increase of Tfh17 and (Tfh2+Tfh17)/Tfh1 ratio and a decrease of Tfr and Tfh1. Rituximab restored the Tfh polarization to that of healthy controls. There was a trend toward a similar result for azathioprine and mycophenolate mofetil. Our results suggest that NMOSD patients present an impaired balance in Tfh subsets favoring B-cell differentiation which may explain the sustained antibody production. These findings provide new insights into the pathophysiology of NMOSD, and further suggest that Tfh and Tfr subsets could be considered as potential therapeutic target in NMOSD because of their upstream role in antibody production.
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spelling pubmed-68776012019-12-04 The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and Restored by Rituximab Nicolas, Philippe Ruiz, Anne Cobo-Calvo, Alvaro Fiard, Guillaume Giraudon, Pascale Vukusic, Sandra Marignier, Romain Front Immunol Immunology Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe auto-immune disease of the central nervous system driven by pathogenic antibodies mainly directed against aquaporin-4 (AQP4-Ab). Treatment of NMOSD currently relies on immunosuppressants (mycophenolate mofetil, azathioprine) or B-cell-depleting therapy (rituximab). B-cell differentiation into antibody-producing cells requires T follicular helper cells (Tfh). There are several Tfh subsets that differentially affect B-cell differentiation; Tfh2 and Tfh17 subsets strongly support B-cell differentiation. By contrast, Tfh1 lack this capacity and T follicular regulatory cells (Tfr), inhibit B-cell differentiation into antibody-producing cells. We performed a broad characterization of circulating Tfh subsets in 25 NMOSD patients and analyzed the impact of different treatments on these subsets. Untreated NMOSD patients presented a Tfh polarization toward excessive B-helper Tfh subsets with an increase of Tfh17 and (Tfh2+Tfh17)/Tfh1 ratio and a decrease of Tfr and Tfh1. Rituximab restored the Tfh polarization to that of healthy controls. There was a trend toward a similar result for azathioprine and mycophenolate mofetil. Our results suggest that NMOSD patients present an impaired balance in Tfh subsets favoring B-cell differentiation which may explain the sustained antibody production. These findings provide new insights into the pathophysiology of NMOSD, and further suggest that Tfh and Tfr subsets could be considered as potential therapeutic target in NMOSD because of their upstream role in antibody production. Frontiers Media S.A. 2019-11-19 /pmc/articles/PMC6877601/ /pubmed/31803192 http://dx.doi.org/10.3389/fimmu.2019.02686 Text en Copyright © 2019 Nicolas, Ruiz, Cobo-Calvo, Fiard, Giraudon, Vukusic and Marignier. http://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 Immunology
Nicolas, Philippe
Ruiz, Anne
Cobo-Calvo, Alvaro
Fiard, Guillaume
Giraudon, Pascale
Vukusic, Sandra
Marignier, Romain
The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and Restored by Rituximab
title The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and Restored by Rituximab
title_full The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and Restored by Rituximab
title_fullStr The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and Restored by Rituximab
title_full_unstemmed The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and Restored by Rituximab
title_short The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and Restored by Rituximab
title_sort balance in t follicular helper cell subsets is altered in neuromyelitis optica spectrum disorder patients and restored by rituximab
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877601/
https://www.ncbi.nlm.nih.gov/pubmed/31803192
http://dx.doi.org/10.3389/fimmu.2019.02686
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