title: Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod.
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.
authors.affiliation: Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria. a.harrer@salk.at.
authors.forename: Andrea
authors.initials: A
authors.lastname: Harrer
authors.affiliation: Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria. p.wipfler@salk.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Wipfler
authors.affiliation: Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria. georg.pilz@salk.at.
authors.forename: Georg
authors.initials: G
authors.lastname: Pilz
authors.affiliation: Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria. k.oppermann@salk.at.
authors.forename: Katrin
authors.initials: K
authors.lastname: Oppermann
authors.affiliation: Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Haschke-Becher
authors.affiliation: Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria. s.afazel@salk.at.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Afazel
authors.affiliation: Department of Neurology, A.ö. Krankenhaus Zell am See, Teaching Hospital of the Paracelsus Medical University, 5700 Zell am See, Austria. joerg.kraus@kh-zellamsee.at.|Research Institute of Neurointervention, Paracelsus Medical University, 5020 Salzburg, Austria. joerg.kraus@kh-zellamsee.at.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kraus
authors.affiliation: Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria. e.trinka@salk.at.
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
authors.affiliation: Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria. j.sellner@salk.at.|Department of Neurology, Klinikum rechts der Isar, Technische Universität, 81675 München, Germany. j.sellner@salk.at.
authors.forename: Johann
authors.initials: J
authors.lastname: Sellner
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D000068876:Fingolimod Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use; D006562:Herpes Zoster / Q000150:complications* / Q000276:immunology* / Q000821:virology; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D010641:Phenotype; D014775:Virus Activation / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: VZV reactivation; cerebrospinal fluid; fingolimod; immune reconstitution; peripheral blood; treatment discontinuation