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Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod

Fingolimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for the treatment of relapsing forms of multiple sclerosis (MS). The interference with S1P signaling leads to retention particularly of chemokine receptor-7 (CCR7) expressing T cells in lymph nodes. The immunological b...

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Autores principales: Harrer, Andrea, Wipfler, Peter, Pilz, Georg, Oppermann, Katrin, Haschke-Becher, Elisabeth, Afazel, Shahrzad, Kraus, Jörg, Trinka, Eugen, Sellner, Johann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613283/
https://www.ncbi.nlm.nih.gov/pubmed/26378517
http://dx.doi.org/10.3390/ijms160921832
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author Harrer, Andrea
Wipfler, Peter
Pilz, Georg
Oppermann, Katrin
Haschke-Becher, Elisabeth
Afazel, Shahrzad
Kraus, Jörg
Trinka, Eugen
Sellner, Johann
author_facet Harrer, Andrea
Wipfler, Peter
Pilz, Georg
Oppermann, Katrin
Haschke-Becher, Elisabeth
Afazel, Shahrzad
Kraus, Jörg
Trinka, Eugen
Sellner, Johann
author_sort Harrer, Andrea
collection PubMed
description Fingolimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for the treatment of relapsing forms of multiple sclerosis (MS). The interference with S1P signaling leads to retention particularly of chemokine receptor-7 (CCR7) expressing T cells in lymph nodes. The immunological basis of varicella zoster virus (VZV) infections during fingolimod treatment is unclear. Here, we studied the dynamics of systemic and intrathecal immune responses associated with symptomatic VZV reactivation including cessation of fingolimod and initiation of antiviral therapy. Key features in peripheral blood were an about two-fold increase of VZV-specific IgG at diagnosis of VZV reactivation as compared to the previous months, a relative enrichment of effector CD4+ T cells (36% versus mean 12% in controls), and an accelerated reconstitution of absolute lymphocytes counts including a normalized CD4+/CD8+ ratio and reappearance of CCR7+ T cells. In cerebrospinal fluid (CSF) the lymphocytic pleocytosis and CD4+/CD8+ ratios at diagnosis of reactivation and after nine days of fingolimod discontinuation remained unchanged. During this time CCR7+ T cells were not observed in CSF. Further research into fingolimod-associated VZV reactivation and immune reconstitution is mandatory to prevent morbidity and mortality associated with this potentially life-threatening condition.
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spelling pubmed-46132832015-10-26 Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod Harrer, Andrea Wipfler, Peter Pilz, Georg Oppermann, Katrin Haschke-Becher, Elisabeth Afazel, Shahrzad Kraus, Jörg Trinka, Eugen Sellner, Johann Int J Mol Sci Article Fingolimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for the treatment of relapsing forms of multiple sclerosis (MS). The interference with S1P signaling leads to retention particularly of chemokine receptor-7 (CCR7) expressing T cells in lymph nodes. The immunological basis of varicella zoster virus (VZV) infections during fingolimod treatment is unclear. Here, we studied the dynamics of systemic and intrathecal immune responses associated with symptomatic VZV reactivation including cessation of fingolimod and initiation of antiviral therapy. Key features in peripheral blood were an about two-fold increase of VZV-specific IgG at diagnosis of VZV reactivation as compared to the previous months, a relative enrichment of effector CD4+ T cells (36% versus mean 12% in controls), and an accelerated reconstitution of absolute lymphocytes counts including a normalized CD4+/CD8+ ratio and reappearance of CCR7+ T cells. In cerebrospinal fluid (CSF) the lymphocytic pleocytosis and CD4+/CD8+ ratios at diagnosis of reactivation and after nine days of fingolimod discontinuation remained unchanged. During this time CCR7+ T cells were not observed in CSF. Further research into fingolimod-associated VZV reactivation and immune reconstitution is mandatory to prevent morbidity and mortality associated with this potentially life-threatening condition. MDPI 2015-09-10 /pmc/articles/PMC4613283/ /pubmed/26378517 http://dx.doi.org/10.3390/ijms160921832 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Harrer, Andrea
Wipfler, Peter
Pilz, Georg
Oppermann, Katrin
Haschke-Becher, Elisabeth
Afazel, Shahrzad
Kraus, Jörg
Trinka, Eugen
Sellner, Johann
Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod
title Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod
title_full Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod
title_fullStr Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod
title_full_unstemmed Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod
title_short Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod
title_sort adaptive immune responses in a multiple sclerosis patient with acute varicella-zoster virus reactivation during treatment with fingolimod
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613283/
https://www.ncbi.nlm.nih.gov/pubmed/26378517
http://dx.doi.org/10.3390/ijms160921832
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