The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Elevated Tribbles homolog 2–specific antibody levels in narcolepsy patients
Open accessAbstract
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.
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Self-citationReduced Number of Hypocretin Neurons in Human Narcolepsy
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Self-citationGenetic Ablation of Orexin Neurons in Mice Results in Narcolepsy, Hypophagia, and Obesity
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Self-citationDistinct Narcolepsy Syndromes in Orexin Receptor-2 and Orexin Null Mice
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Cited by
Control of sleep and wakefulness
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Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in china
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The neurobiological basis of narcolepsy
Mahoney, C. E., Cogswell, A., Koralnik, I. J., & Scammell, T. E. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0097-x · Cited by 289
Metadata
- Authors
- Cvetkovic-Lopes, V., Bayer, L., Dorsaz, S., Maret, S., Pradervand, S., Dauvilliers, Y., Lecendreux, M., Lammers, G.-J., Donjacour, C. E. H. M., Du Pasquier, R. A., Pfister, C., Petit, B., Hor, H., Mühlethaler, M., & Tafti, M.
- Venue
- Journal of Clinical Investigation
- Published
- 2010-03-01
- Volume
- 120
- Issue
- 3
- Pages
- 713-719
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1965784748
- Cited by
- 307
- References
- 28
- FWCI
- 19.91
- Type
- journal article
- Language
- en
- Open access
- green
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- Cvetkovic-Lopes, V., Bayer, L., Dorsaz, S., Maret, S., Pradervand, S., Dauvilliers, Y., Lecendreux, M., Lammers, G.-J., Donjacour, C. E. H. M., Du Pasquier, R. A., Pfister, C., Petit, B., Hor, H., Mühlethaler, M., & Tafti, M. (2010). Elevated Tribbles homolog 2–specific antibody levels in narcolepsy patients. Journal of Clinical Investigation. https://doi.org/10.1172/jci41366
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