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Related Concept Videos

Narcolepsy01:07

Narcolepsy

Narcolepsy is a chronic sleep disorder characterized by pervasive, uncontrolled sleepiness and other sleep disturbances. One of its hallmark symptoms is an abrupt transition to REM sleep upon falling asleep, which causes symptoms typically associated with this phase to occur unexpectedly during wakefulness. These include the following symptoms, which typically last from a minute or two to half an hour.
Sleep-Wake Cycles01:24

Sleep-Wake Cycles

Sleep is an essential physiological process vital to maintaining overall well-being. The reticular activating system (RAS), a network of neurons in the brainstem, regulates wakefulness and sleep. While it may seem passive, sleep consists of distinct cycles, each with its unique characteristics and functions. Two key sleep phases are non-rapid eye movement (NREM) and  rapid eye movement (REM).
NREM Sleep
NREM sleep comprises four progressive stages that seamlessly merge:
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...

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A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
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ImmunoChip study implicates antigen presentation to T cells in narcolepsy.

Juliette Faraco1, Ling Lin, Birgitte Rahbek Kornum

  • 1Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, California, USA.

Plos Genetics
|March 6, 2013
PubMed
Summary
This summary is machine-generated.

Genetic analysis supports a post-infectious autoimmune cause for narcolepsy/hypocretin deficiency. Key genetic loci outside the HLA region, including CTSH and TNFSF4, were linked to increased narcolepsy risk.

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Area of Science:

  • Immunogenetics
  • Neuroimmunology
  • Human Genetics

Background:

  • Narcolepsy/hypocretin deficiency is increasingly understood as a post-infectious autoimmune disorder.
  • Genetic and environmental factors are implicated in its pathophysiology.
  • The Human Leukocyte Antigen (HLA) region is known to be associated with autoimmune diseases.

Purpose of the Study:

  • To investigate genetic associations with narcolepsy/hypocretin deficiency outside the HLA region.
  • To identify specific susceptibility loci contributing to this autoimmune condition.
  • To further elucidate the autoimmune basis of narcolepsy.

Main Methods:

  • Genotyping of 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls of European ancestry.
  • Utilized a custom ImmunoChip array to analyze loci associated with autoimmune and inflammatory diseases.
  • Performed statistical analysis to identify significant genetic associations with disease risk.

Main Results:

  • Three novel genetic loci outside the HLA region on chromosome 6 were significantly associated with narcolepsy risk.
  • Strong association found in the T cell receptor alpha (TRA@) locus.
  • Variants in Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4/OX40L) also reached genome-wide significance.

Conclusions:

  • These findings highlight the role of specific genes, CTSH and TNFSF4, in narcolepsy susceptibility.
  • The results reinforce the importance of HLA Class II-mediated antigen presentation in T cell activation in narcolepsy.
  • The study provides further evidence for an autoimmune etiology of narcolepsy/hypocretin deficiency.