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

• Published in: Sleep (New York, N.Y.) Vol. 40; no. 3
• Main Authors: Ramberger, Melanie, Högl, Birgit, Stefani, Ambra, Mitterling, Thomas, Reindl, Markus, Lutterotti, Andreas
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.03.2017
• Subjects: Adolescent; Adult; Aged; Amino Acid Sequence; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell division; Cells, Cultured; Child; Cytokines; Female; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - pharmacology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lymphocytes; Male; Middle Aged; Narcolepsy - blood; Narcolepsy - immunology; Neurons - drug effects; Neurons - immunology; Neurons - metabolism; Orexins - genetics; Orexins - pharmacology; Original; Sleep disorders; T cell receptors; Young Adult; Narcolepsy type 1; orexin/hypocretin; CD4; autoimmune disease; HLA-DQB106:02; T-cell proliferation; CD4+ T-cell proliferation
• ISSN: 0161-8105; 1550-9109
• DOI: 10.1093/sleep/zsw070

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.