학술논문
ImmunoChip study implicates antigen presentation to T cells in narcolepsy.
Document Type
article
Author
Juliette Faraco; Ling Lin; Birgitte Rahbek Kornum; Eimear E Kenny; Gosia Trynka; Mali Einen; Tom J Rico; Peter Lichtner; Yves Dauvilliers; Isabelle Arnulf; Michel Lecendreux; Sirous Javidi; Peter Geisler; Geert Mayer; Fabio Pizza; Francesca Poli; Giuseppe Plazzi; Sebastiaan Overeem; Gert Jan Lammers; David Kemlink; Karel Sonka; Sona Nevsimalova; Guy Rouleau; Alex Desautels; Jacques Montplaisir; Birgit Frauscher; Laura Ehrmann; Birgit Högl; Poul Jennum; Patrice Bourgin; Rosa Peraita-Adrados; Alex Iranzo; Claudio Bassetti; Wei-Min Chen; Patrick Concannon; Susan D Thompson; Vincent Damotte; Bertrand Fontaine; Maxime Breban; Christian Gieger; Norman Klopp; Panos Deloukas; Cisca Wijmenga; Joachim Hallmayer; Suna Onengut-Gumuscu; Stephen S Rich; Juliane Winkelmann; Emmanuel Mignot
Source
PLoS Genetics, Vol 9, Iss 2, p e1003270 (2013)
Subject
Language
English
ISSN
1553-7390
1553-7404
1553-7404
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.