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J Exp Med. 2016 Nov 14;213(12):2621-2633. Epub 2016 Nov 7.

High-dimensional single-cell analysis reveals the immune signature of narcolepsy.

Author information

1
Institute of Experimental Immunology, University of Zurich, CH-8057 Zurich, Switzerland.
2
Centre de Physiopathologie Toulouse-Purpan, Université de Toulouse, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, UPS, 31024 Toulouse, France.
3
Institute of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
4
SIB Swiss Institute of Bioinformatics, University of Zurich, CH-8057 Zurich, Switzerland.
5
National Reference Center for Orphan Diseases, Narcolepsy, Idiopathic hypersomnia and Kleine-Levin Syndrome, Department of Neurology, Gui-de-Chauliac Hospital, CHU de Montpellier, Institut National de la Santé et de la Recherche Médicale U1061, 34090 Montpellier, France.
6
Centre de Physiopathologie Toulouse-Purpan, Université de Toulouse, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, UPS, 31024 Toulouse, France roland.liblau@inserm.fr becher@immunology.uzh.ch.
7
Institute of Experimental Immunology, University of Zurich, CH-8057 Zurich, Switzerland roland.liblau@inserm.fr becher@immunology.uzh.ch.

Abstract

Narcolepsy type 1 is a devastating neurological sleep disorder resulting from the destruction of orexin-producing neurons in the central nervous system (CNS). Despite its striking association with the HLA-DQB1*06:02 allele, the autoimmune etiology of narcolepsy has remained largely hypothetical. Here, we compared peripheral mononucleated cells from narcolepsy patients with HLA-DQB1*06:02-matched healthy controls using high-dimensional mass cytometry in combination with algorithm-guided data analysis. Narcolepsy patients displayed multifaceted immune activation in CD4+ and CD8+ T cells dominated by elevated levels of B cell-supporting cytokines. Additionally, T cells from narcolepsy patients showed increased production of the proinflammatory cytokines IL-2 and TNF. Although it remains to be established whether these changes are primary to an autoimmune process in narcolepsy or secondary to orexin deficiency, these findings are indicative of inflammatory processes in the pathogenesis of this enigmatic disease.

PMID:
27821550
PMCID:
PMC5110028
DOI:
10.1084/jem.20160897
[Indexed for MEDLINE]
Free PMC Article

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