Next Article in Journal
A Novel Function of TET2 in CNS: Sustaining Neuronal Survival
Next Article in Special Issue
Early and Degressive Putamen Atrophy in Multiple Sclerosis
Previous Article in Journal
Surface Properties of Squalene/Meibum Films and NMR Confirmation of Squalene in Tears
Previous Article in Special Issue
Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling
Article Menu
Issue 9 (September) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(9), 21832-21845; doi:10.3390/ijms160921832

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

1
Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria
2
Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria
3
Department of Neurology, A.ö. Krankenhaus Zell am See, Teaching Hospital of the Paracelsus Medical University, 5700 Zell am See, Austria
4
Research Institute of Neurointervention, Paracelsus Medical University, 5020 Salzburg, Austria
5
Department of Neurology, Klinikum rechts der Isar, Technische Universität, 81675 München, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Christoph Kleinschnitz
Received: 13 August 2015 / Revised: 1 September 2015 / Accepted: 2 September 2015 / Published: 10 September 2015
(This article belongs to the Special Issue Advances in Multiple Sclerosis)
View Full-Text   |   Download PDF [1779 KB, uploaded 10 September 2015]   |  

Abstract

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. View Full-Text
Keywords: VZV reactivation; fingolimod; treatment discontinuation; immune reconstitution; peripheral blood; cerebrospinal fluid VZV reactivation; fingolimod; treatment discontinuation; immune reconstitution; peripheral blood; cerebrospinal fluid
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Harrer, A.; Wipfler, P.; Pilz, G.; Oppermann, K.; Haschke-Becher, E.; Afazel, S.; Kraus, J.; Trinka, E.; Sellner, J. Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod. Int. J. Mol. Sci. 2015, 16, 21832-21845.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top