Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination

Partinen, Markku; Kornum, Birgitte Rahbek; Plazzi, Giuseppe; Jennum, Poul; Julkunen, Ilkka; Vaarala, Outi

doi:10.1016/s1474-4422(14)70075-4

Cited by 235 publications

(195 citation statements)

References 131 publications

Supporting

Mentioning

188

Contrasting

Unclassified

Order By: Relevance

“…Recent evidence, including the increase in the incidence of narcolepsy after the H1N1 vaccination in 2010, supports a role for autoimmunity in the destruction of HCT neurons [31,32]. Of note, in the current International Classification of Sleep Disorders 3rd Edition (ICSD-3), narcolepsy type 1 (formerly known as Bnarcolepsy with cataplexy^and sometimes referred to as Bhypocretin deficiency syndrome^) is distinguished from narcolepsy type 2 (formerly known as Bnarcolepsy without cataplexy^) on the basis of HCT deficiency [33].…”

Section: Neurological Disorders Of Arousalmentioning

confidence: 99%

Neurobiology of Arousal and Sleep: Updates and Insights Into Neurological Disorders

Lim

Szymusiak

2015

Curr Sleep Medicine Rep

View full text Add to dashboard Cite

Brain activation during wakefulness is sustained by multiple arousal systems. Dysfunction of one or more arousal systems is a feature of neurological disorders associated with hypersomnolence and/or sleep-wake cycle disturbance. Narcolepsy, Alzheimer's disease (AD), Parkinson's disease (PD), and traumatic brain injury appear to involve hypocretin (HCT) and possibly histamine insufficiency as a mechanism related to excessive daytime sleepiness. Loss of cholinergic neurons in AD and of dopamine neurons in PD contributes to sleepwake disturbance. GABAergic neurons in the preoptic hypothalamus and rostral medulla promote sleep through inhibition of arousal systems. Pathology of preoptic sleep regulatory circuits is correlated with sleep disturbance in AD. An unidentified endogenous somnogen that potentiates the actions of gamma-aminobutyric acid (GABA) is present in the cerebrospinal fluid (CSF) of patients with primary hypersomnia.Descending pathways from the dorsal lateral pons to the ventral medulla and spinal cord are responsible for the inhibition of spinal motoneurons during rapid eye movement (REM) sleep and are implicated in human REM sleep behavior disorder.

show abstract

Section: Neurological Disorders Of Arousalmentioning

confidence: 99%

Neurobiology of Arousal and Sleep: Updates and Insights Into Neurological Disorders

Lim

Szymusiak

2015

Curr Sleep Medicine Rep

View full text Add to dashboard Cite

show abstract

“…The prevalence of narcolepsy in the paediatric population remains unknown, but based upon the regional study conducted in the U.S.A., it could affect 20-50 per 100,000 children [5]. Two peaks of onset are suggested, at ages 15-25 years and ages 30-35 years [2].…”

Section: Introductionmentioning

confidence: 99%

Quickly diagnosed and treated prepubertal Type 1 narcolepsy case

Çökmüş

Aydın

Di̇ki̇ci̇³

et al. 2017

Psychiatry and Clinical Psychopharmacology

View full text Add to dashboard Cite

Excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucination are the classic tetrad of narcolepsy. It has been shown that narcolepsy, a chronic and disabling disease, starts in childhood and adolescence rather than adulthood. The International Classification of Sleep Disorder (ICSD-3) classifies narcolepsy into Type 1 (narcolepsy with cataplexy) and Type 2 (narcolepsy without cataplexy). There is low awareness and knowledge of narcolepsy among the general public, primary care physicians, and sleep specialists. It has been shown that the lack of recognition of disease symptoms delayed the diagnosis of narcolepsy from 8.7 to 22.1 years. In this case report, we will discuss the case of Type 1 narcolepsy, which started in the prepubertal period and was diagnosed and treated in a short period of time. ARTICLE HISTORY

show abstract

“…3 The loss of hcrt-producing cells is hypothesized to have an autoimmune basis. 4 One of the genetic associations in narcolepsy is rs2305795, a polymorphism located in the purinergic receptor P2RY11. 5,6 The disease-associated allele of rs2305795 decreases P2RY11 expression and increases the sensitivity of CD8 + T cells to cell death induced by ATP.…”

Section: Introductionmentioning

confidence: 99%

EIF3G is associated with narcolepsy across ethnicities

Holm

Faraco

et al. 2015

Eur J Hum Genet

Self Cite

View full text Add to dashboard Cite

Type 1 narcolepsy, an autoimmune disease affecting hypocretin (orexin) neurons, is strongly associated with HLA-DQB1*06:02. Among polymorphisms associated with the disease is single-nucleotide polymorphism rs2305795 (c.*638G4A) located within the P2RY11 gene. P2RY11 is in a region of synteny conserved in mammals and zebrafish containing PPAN, EIF3G and DNMT1 (DNA methyltransferase 1). As mutations in DNMT1 cause a rare dominant form of narcolepsy in association with deafness, cerebellar ataxia and dementia, we questioned whether the association with P2RY11 in sporadic narcolepsy could be secondary to linkage disequilibrium with DNMT1. Based on genome-wide association data from two cohorts of European and Chinese ancestry, we found that the narcolepsy association signal drops sharply between P2RY11/EIF3G and DNMT1, suggesting that the association with narcolepsy does not extend into the DNMT1 gene region. Interestingly, using transethnic mapping, we identified a novel single-nucleotide polymorphism rs3826784 (c.596-260A4G) in the EIF3G gene also associated with narcolepsy. The disease-associated allele increases EIF3G mRNA expression. EIF3G is located in the narcolepsy risk locus and EIF3G expression correlates with PPAN and P2RY11 expression. This suggests shared regulatory mechanisms that might be affected by the polymorphism and are of relevance to narcolepsy. INTRODUCTIONNarcolepsy with cataplexy (Type 1 narcolepsy) affects 1 in 3000 individuals and is caused by the loss of around 70 000 hypocretin-(hcrt, also known as orexin) producing neurons in the hypothalamus. The disease is strongly associated with HLA-DQB1*06:02 and DQA1*01:02, 1 the T-cell receptor alpha locus 2 and polymorphisms in other immune-related genes. 3 The loss of hcrt-producing cells is hypothesized to have an autoimmune basis. 4 One of the genetic associations in narcolepsy is rs2305795, a polymorphism located in the purinergic receptor P2RY11. 5,6 The disease-associated allele of rs2305795 decreases P2RY11 expression and increases the sensitivity of CD8 + T cells to cell death induced by ATP. Interestingly, we also recently found that missense mutation in exon 21 of the DNA methyltransferase 1 (DNMT1) gene causes a rare hereditary form of narcolepsy-associated deafness, cerebellar ataxia and eventually dementia (ADCA-DN). 7 As the P2RY11 and DNMT1 genes are located in close proximity (within 18 kb) on chromosome 19, we hypothesized that the two signals could be related at the pathophysiological level. In support of this hypothesis, Kornum et al. 5 observed a correlation between P2RY11 and DNMT1 expression in peripheral blood mononuclear cells (PBMCs) of both patients and healthy controls. These findings made us question whether the association with P2RY11 in spontaneous narcolepsy could be secondary to linkage disequilibrium (LD) with DNMT1. In the original study, Kornum et al. 5 fine-mapped the locus using seven single-nucleotide polymorphisms (SNPs) and reported an association between DNMT1 and narcolepsy in individuals of European anc...

show abstract

Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination

Cited by 235 publications

References 131 publications

Neurobiology of Arousal and Sleep: Updates and Insights Into Neurological Disorders

Neurobiology of Arousal and Sleep: Updates and Insights Into Neurological Disorders

Quickly diagnosed and treated prepubertal Type 1 narcolepsy case

EIF3G is associated with narcolepsy across ethnicities

Contact Info

Product

Resources

About