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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02686/full |
| _version_ | 1818281272158453760 |
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| author | Philippe Nicolas Philippe Nicolas Anne Ruiz Alvaro Cobo-Calvo Alvaro Cobo-Calvo Guillaume Fiard Pascale Giraudon Sandra Vukusic Sandra Vukusic Romain Marignier Romain Marignier Romain Marignier |
| author_facet | Philippe Nicolas Philippe Nicolas Anne Ruiz Alvaro Cobo-Calvo Alvaro Cobo-Calvo Guillaume Fiard Pascale Giraudon Sandra Vukusic Sandra Vukusic Romain Marignier Romain Marignier Romain Marignier |
| author_sort | Philippe Nicolas |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T00:02:29Z |
| format | Article |
| id | doaj.art-9214212a9b1d45be85f5c522c1eae093 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T00:02:29Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9214212a9b1d45be85f5c522c1eae0932022-12-22T00:06:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-11-011010.3389/fimmu.2019.02686467007The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and Restored by RituximabPhilippe Nicolas0Philippe Nicolas1Anne Ruiz2Alvaro Cobo-Calvo3Alvaro Cobo-Calvo4Guillaume Fiard5Pascale Giraudon6Sandra Vukusic7Sandra Vukusic8Romain Marignier9Romain Marignier10Romain Marignier11Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, et Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, FranceCentre de Recherche en Neurosciences de Lyon, INSERM U1028-CNRS UMR5292-UCBL, Bron, FranceCentre de Recherche en Neurosciences de Lyon, INSERM U1028-CNRS UMR5292-UCBL, Bron, FranceService de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, et Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, FranceCentre de Recherche en Neurosciences de Lyon, INSERM U1028-CNRS UMR5292-UCBL, Bron, FranceNeuroBioTec, Hôpital Neurologique Pierre Wertheimer, Bron, FranceCentre de Recherche en Neurosciences de Lyon, INSERM U1028-CNRS UMR5292-UCBL, Bron, FranceService de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, et Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, FranceCentre de Recherche en Neurosciences de Lyon, INSERM U1028-CNRS UMR5292-UCBL, Bron, FranceService de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, et Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, FranceCentre de Recherche en Neurosciences de Lyon, INSERM U1028-CNRS UMR5292-UCBL, Bron, FranceNeuroBioTec, Hôpital Neurologique Pierre Wertheimer, Bron, FranceNeuromyelitis 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.02686/fullneuromyelitis optica spectrum disorderT follicular helper cellsT follicular regulatory cellsB cellsrituximab |
| spellingShingle | Philippe Nicolas Philippe Nicolas Anne Ruiz Alvaro Cobo-Calvo Alvaro Cobo-Calvo Guillaume Fiard Pascale Giraudon Sandra Vukusic Sandra Vukusic Romain Marignier Romain Marignier Romain Marignier The Balance in T Follicular Helper Cell Subsets Is Altered in Neuromyelitis Optica Spectrum Disorder Patients and Restored by Rituximab Frontiers in Immunology neuromyelitis optica spectrum disorder T follicular helper cells T follicular regulatory cells B cells 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 | neuromyelitis optica spectrum disorder T follicular helper cells T follicular regulatory cells B cells rituximab |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02686/full |
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