1. ImmunoChip study implicates antigen presentation to T cells in narcolepsy.
- Author
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Faraco J, Lin L, Kornum BR, Kenny EE, Trynka G, Einen M, Rico TJ, Lichtner P, Dauvilliers Y, Arnulf I, Lecendreux M, Javidi S, Geisler P, Mayer G, Pizza F, Poli F, Plazzi G, Overeem S, Lammers GJ, Kemlink D, Sonka K, Nevsimalova S, Rouleau G, Desautels A, Montplaisir J, Frauscher B, Ehrmann L, Högl B, Jennum P, Bourgin P, Peraita-Adrados R, Iranzo A, Bassetti C, Chen WM, Concannon P, Thompson SD, Damotte V, Fontaine B, Breban M, Gieger C, Klopp N, Deloukas P, Wijmenga C, Hallmayer J, Onengut-Gumuscu S, Rich SS, Winkelmann J, and Mignot E
- Subjects
- Genetic Association Studies, HLA Antigens genetics, HLA Antigens immunology, Humans, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins immunology, Intracellular Signaling Peptides and Proteins metabolism, Narcolepsy immunology, Narcolepsy physiopathology, Neuropeptides genetics, Neuropeptides immunology, Neuropeptides metabolism, Orexins, White People, Antigen Presentation genetics, Antigen Presentation immunology, Autoimmune Diseases genetics, Autoimmune Diseases immunology, Autoimmune Diseases metabolism, Narcolepsy genetics, Receptors, Antigen, T-Cell, alpha-beta genetics, Receptors, Antigen, T-Cell, alpha-beta metabolism
- Abstract
Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2013
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