Header

UZH-Logo

Maintenance Infos

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


Hartmann, Felix J; Bernard-Valnet, Raphaël; Quériault, Clémence; Mrdjen, Dunja; Weber, Lukas M; Galli, Edoardo; Krieg, Carsten; Robinson, Mark D; Nguyen, Xuan-Hung; Dauvilliers, Yves; Liblau, Roland S; Becher, Burkhard (2016). High-dimensional single-cell analysis reveals the immune signature of narcolepsy. Journal of Experimental Medicine, 213(12):2621-2633.

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.

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.

Statistics

Citations

Dimensions.ai Metrics
10 citations in Web of Science®
14 citations in Scopus®
14 citations in Microsoft Academic
Google Scholar™

Altmetrics

Downloads

104 downloads since deposited on 16 Dec 2016
78 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:14 November 2016
Deposited On:16 Dec 2016 09:48
Last Modified:19 Aug 2018 05:42
Publisher:Rockefeller University Press
ISSN:0022-1007
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1084/jem.20160897
PubMed ID:27821550
Project Information:
  • : FunderSNSF
  • : Grant ID316030_150768
  • : Project TitleThe use of Mass-cytometry in multi-parameter immune cell analysis
  • : FunderSNSF
  • : Grant ID310030_146130
  • : Project TitleThe role of the NF?B-inducing kinase NIK in the development and function of cellular immunity

Download

Download PDF  'High-dimensional single-cell analysis reveals the immune signature of narcolepsy'.
Preview
Content: Published Version
Filetype: PDF
Size: 2MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)