Elevated Tribbles homolog 2-specific antibody levels in narcolepsy patients.
Details
Serval ID
serval:BIB_6F1CF4DFB5CB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Elevated Tribbles homolog 2-specific antibody levels in narcolepsy patients.
Journal
Journal of Clinical Investigation
ISSN
1558-8238[electronic], 0021-9738[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
120
Number
3
Pages
713-719
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and attacks of muscle atonia triggered by strong emotions (cataplexy). Narcolepsy is caused by hypocretin (orexin) deficiency, paralleled by a dramatic loss in hypothalamic hypocretin-producing neurons. It is believed that narcolepsy is an autoimmune disorder, although definitive proof of this, such as the presence of autoantibodies, is still lacking. We engineered a transgenic mouse model to identify peptides enriched within hypocretin-producing neurons that could serve as potential autoimmune targets. Initial analysis indicated that the transcript encoding Tribbles homolog 2 (Trib2), previously identified as an autoantigen in autoimmune uveitis, was enriched in hypocretin neurons in these mice. ELISA analysis showed that sera from narcolepsy patients with cataplexy had higher Trib2-specific antibody titers compared with either normal controls or patients with idiopathic hypersomnia, multiple sclerosis, or other inflammatory neurological disorders. Trib2-specific antibody titers were highest early after narcolepsy onset, sharply decreased within 2-3 years, and then stabilized at levels substantially higher than that of controls for up to 30 years. High Trib2-specific antibody titers correlated with the severity of cataplexy. Serum of a patient showed specific immunoreactivity with over 86% of hypocretin neurons in the mouse hypothalamus. Thus, we have identified reactive autoantibodies in human narcolepsy, providing evidence that narcolepsy is an autoimmune disorder.
Keywords
Animals, Autoantibodies/blood, Autoantibodies/immunology, Autoantigens/genetics, Autoantigens/immunology, Autoimmune Diseases/blood, Autoimmune Diseases/genetics, Female, Humans, Hypothalamus/immunology, Hypothalamus/metabolism, Intracellular Signaling Peptides and Proteins/genetics, Intracellular Signaling Peptides and Proteins/immunology, Male, Mice, Mice, Transgenic, Narcolepsy/blood, Narcolepsy/genetics, Neurons/immunology, Neurons/metabolism, Neuropeptides/genetics, Neuropeptides/immunology, Protein-Serine-Threonine Kinases/genetics, Protein-Serine-Threonine Kinases/immunology, Severity of Illness Index, Sleep Initiation and Maintenance Disorders/blood, Sleep Initiation and Maintenance Disorders/genetics, Time Factors
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2011 13:42
Last modification date
20/08/2019 15:28