title: CD4+ T-Cell Reactivity to Orexin/Hypocretin in Patients With Narcolepsy Type 1.
abstract: Narcolepsy type 1 is accompanied by a selective loss of orexin/hypocretin (hcrt) neurons in the lateral hypothalamus caused by yet unknown mechanisms. Epidemiologic and genetic associations strongly suggest an immune-mediated pathogenesis of the disease.
  
  
  
  We compared specific T-cell reactivity to orexin/hcrt peptides in peripheral blood mononuclear cells of narcolepsy type 1 patients to healthy controls by a carboxyfluorescein succinimidyl ester proliferation assay. Orexin/hcrt-specific T-cell reactivity was also determined by cytokine (interferon gamma and granulocyte-macrophage colony-stimulating factor) analysis. Individuals were considered as responders if the cell division index of CD3+CD4+ T cells and both stimulation indices of cytokine secretion exceeded the cutoff 3. Additionally, T-cell reactivity to orexin/hcrt had to be confirmed by showing reactivity to single peptides present in different peptide pools.
  
  
  
  Using these criteria, 3/15 patients (20%) and 0/13 controls (0%) showed orexin/hcrt-specific CD4+ T-cell proliferation (p = .2262). The heterogeneous reactivity pattern did not allow the identification of a preferential target epitope.
  
  
  
  A significant role of orexin/hcrt-specific T cells in narcolepsy type 1 patients could not be confirmed in this study. Further studies are needed to assess the exact role of CD4+ T cells and possible target antigens in narcolepsy type 1 patients.
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.|Thomas Mitterling is now at Department of Neurology, Wagner-Jauregg Hospital, Wagner-Jauregg Weg 15, A-4020 Linz, Austria.|Andreas Lutterotti is now at Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Ramberger
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.|Thomas Mitterling is now at Department of Neurology, Wagner-Jauregg Hospital, Wagner-Jauregg Weg 15, A-4020 Linz, Austria.|Andreas Lutterotti is now at Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland.
authors.forename: Birgit
authors.initials: B
authors.lastname: Högl
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.|Thomas Mitterling is now at Department of Neurology, Wagner-Jauregg Hospital, Wagner-Jauregg Weg 15, A-4020 Linz, Austria.|Andreas Lutterotti is now at Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland.
authors.forename: Ambra
authors.initials: A
authors.lastname: Stefani
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.|Thomas Mitterling is now at Department of Neurology, Wagner-Jauregg Hospital, Wagner-Jauregg Weg 15, A-4020 Linz, Austria.|Andreas Lutterotti is now at Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mitterling
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.|Thomas Mitterling is now at Department of Neurology, Wagner-Jauregg Hospital, Wagner-Jauregg Weg 15, A-4020 Linz, Austria.|Andreas Lutterotti is now at Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.|Thomas Mitterling is now at Department of Neurology, Wagner-Jauregg Hospital, Wagner-Jauregg Weg 15, A-4020 Linz, Austria.|Andreas Lutterotti is now at Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lutterotti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000097:blood* / Q000276:immunology*; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000068797:Orexins / Q000235:genetics / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000068797:Orexins
keywords: CD4+ T-cell proliferation; HLA-DQB1*06:02.; Narcolepsy type 1; autoimmune disease; orexin/hypocretin