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CD4+ T-Cell Reactivity to Orexin/Hypocretin in Patients With Narcolepsy Type 1

Ramberger, Melanie ; Högl, Birgit ; Stefani, Ambra ; Mitterling, Thomas ; Reindl, Markus ; Lutterotti, Andreas

In: SLEEP, 2016, vol. 40, no. 3, p. -

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    Titre
    • CD4+ T-Cell Reactivity to Orexin/Hypocretin in Patients With Narcolepsy Type 1
    Auteur
    • Ramberger, Melanie. Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
    • Högl, Birgit. Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
    • Stefani, Ambra. Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
    • Mitterling, Thomas. Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
    • Reindl, Markus. Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
    • Lutterotti, Andreas. Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
    Type de document
    • Postprint
    Identifiant OAI-PMH
    • oai:doc.rero.ch:331524
    Summary
    Abstract Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.