Open Access
Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination
Markku Partinen,Birgitte Rahbek Kornum,Giuseppe Plazzi,Poul Jennum,Ilkka Julkunen,Ilkka Julkunen,Outi Vaarala +6 more
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TLDR
In this paper, an H1N1 virus-derived antigen might be the trigger for narcolepsy, which is a sleep disorder characterized by loss of hypothalamic hypocretin (orexin) neurons and other risk genes such as T-cell-receptor α chain and purinergic receptor subtype 2Y11.Abstract:
Summary Narcolepsy is a sleep disorder characterised by loss of hypothalamic hypocretin (orexin) neurons. The prevalence of narcolepsy is about 30 per 100 000 people, and typical age at onset is 12–16 years. Narcolepsy is strongly associated with the HLA-DQB1*06:02 genotype, and has been thought of as an immune-mediated disease. Other risk genes, such as T-cell-receptor α chain and purinergic receptor subtype 2Y11, are also implicated. Interest in narcolepsy has increased since the epidemiological observations that H1N1 infection and vaccination are potential triggering factors, and an increase in the incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010 from Sweden and Finland supports the immune-mediated pathogenesis. Epidemiological observations from studies in China also suggest a role for H1N1 virus infections as a trigger for narcolepsy. Although the pathological mechanisms are unknown, an H1N1 virus-derived antigen might be the trigger.read more
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Journal ArticleDOI
Molecular mimicry and autoimmunity
Manuel Rojas,Paula Restrepo-Jiménez,Diana M. Monsalve,Yovana Pacheco,Yeny Acosta-Ampudia,Carolina Ramírez-Santana,Patrick S.C. Leung,Aftab A Ansari,M. Eric Gershwin,Juan-Manuel Anaya +9 more
TL;DR: Studies on the role of autoreactive T-cells that are generated secondary to molecular mimicry, the diversity of the T-cell receptor repertoires of auto-reactiveT-cells, the roles of exposure to cryptic antigens, the generation of autoimmune B-cell responses, the interaction of microbiota and chemical adjuvants with the host immune systems all provide clues in advancing the understanding of the molecular mechanisms involved in the evolving concept of Molecular mimicry.
Journal ArticleDOI
Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment.
Claudio L. Bassetti,Antoine Roger Adamantidis,Denis Burdakov,Denis Burdakov,Denis Burdakov,Fang Han,Ulf Kallweit,Ramin Khatami,Frits Koning,Brigitte R. Kornum,Gert Jan Lammers,Roland S. Liblau,Pierre H. Luppi,Pierre H. Luppi,Geert Mayer,T. Pollmacher,Takeshi Sakurai,Federica Sallusto,Federica Sallusto,Thomas E. Scammell,Mehdi Tafti,Yves Dauvilliers,Yves Dauvilliers +22 more
TL;DR: Current understanding of how genetic, environmental and immune-related factors contribute to a prominent orexin signalling deficiency in patients with NT1 are focused on, along with uncertainties concerning the ‘narcoleptic borderland’, including narcolepsy type 2 (NT2).
Journal ArticleDOI
The hidden burden of influenza: A review of the extra-pulmonary complications of influenza infection
TL;DR: A comprehensive MEDLINE literature review of articles pertaining to extra‐pulmonary complications of influenza infection, using organ‐specific search terms, yielded 218 articles including case reports, epidemiologic investigations, and autopsy studies that were reviewed to determine the clinical involvement of other organs.
Journal ArticleDOI
Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction
TL;DR: In this review, the concept of molecular mimicry and its application in explaining post vaccination autoimmune phenomena is addressed and the principal examples of the influenza, hepatitis B, and human papilloma virus vaccines, all suspected to induce autoimmunity via Molecular mimicry are reviewed.
Journal ArticleDOI
T cells in patients with narcolepsy target self-antigens of hypocretin neurons
Daniela Latorre,Ulf Kallweit,Eric Armentani,Mathilde Foglierini,Mathilde Foglierini,Federico Mele,Antonino Cassotta,Antonino Cassotta,Sandra Jovic,David Jarrossay,Johannes Mathis,Francesco Zellini,Burkhard Becher,Antonio Lanzavecchia,Ramin Khatami,Mauro Manconi,Mehdi Tafti,Claudio L. Bassetti,Federica Sallusto,Federica Sallusto +19 more
TL;DR: The detection of hypocretin-specific autoreactive CD4+ and CD8+ T cells in patients with narcolepsy reveals the autoimmune aetiology of this disorder and provides a basis for rapid diagnosis and treatment of this disease.
References
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Journal ArticleDOI
Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior
Takeshi Sakurai,Akira Amemiya,Makoto Ishii,Ichiyo Matsuzaki,Richard M. Chemelli,Hirokazu Tanaka,S. Clay Williams,James A. Richardson,Gerald P. Kozlowski,Shelagh Wilson,Jonathan R.S. Arch,Robin E. Buckingham,Andrea C. Haynes,Steven A. Carr,Roland S. Annan,Dean E. McNulty,Wu Schyong Liu,Jonathan A. Terrett,Nabil Elshourbagy,Derk J. Bergsma,Masashi Yanagisawa +20 more
TL;DR: Two novel neuropeptides are identified, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors in the hypothalamus of rats.
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The International Classification of Sleep Disorders: Diagnostic and Coding Manual
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The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity
L de Lecea,Thomas S. Kilduff,Christelle Peyron,Xiao-Bing Gao,Pamela E. Foye,Patria E. Danielson,C. Fukuhara,Elena Battenberg,Vigdis T. Gautvik,Frederick S. Bartlett,Wayne N. Frankel,A. N. van den Pol,Floyd E. Bloom,Kaare M. Gautvik,J G Sutcliffe +14 more
TL;DR: A hypothalamus-specific mRNA is described that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin, suggesting that the hypocretins function within the CNS as neurotransmitters.
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Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation
Richard M. Chemelli,Jon T. Willie,Christopher M. Sinton,Joel K. Elmquist,Thomas E. Scammell,Charlotte E. Lee,James A. Richardson,S. Clay Williams,Yumei Xiong,Yaz Y. Kisanuki,Thomas Fitch,Masamitsu Nakazato,Robert E. Hammer,Clifford B. Saper,Masashi Yanagisawa +14 more
TL;DR: It is proposed that orexin regulates sleep/wakefulness states, and that Orexin knockout mice are a model of human narcolepsy, a disorder characterized primarily by rapid eye movement (REM) sleep dysregulation.
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The Sleep Disorder Canine Narcolepsy Is Caused by a Mutation in the Hypocretin (Orexin) Receptor 2 Gene
Ling Lin,Juliette Faraco,Robin Li,Hiroshi Kadotani,William J. Rogers,X. Lin,Xiaohong Qiu,Pieter J. de Jong,Seiji Nishino,Emmanuel Mignot +9 more
TL;DR: It is determined that canine narcolepsy is caused by disruption of the hypocretin (orexin) receptor 2 gene (Hcrtr2) and this result identifies hypocretins as major sleep-modulating neurotransmitters and opens novel potential therapeutic approaches for Narcoleptic patients.