ImmunoChip study implicates antigen presentation to T cells in narcolepsy.

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.

• Authors: 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
• Journal: PLoS genetics (PLoS Genet) Vol. 9 Issue 2 Pg. e1003270 ( 2013) ISSN: 1553-7404 [Electronic] United States
• PMID: 23459209 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• HLA Antigens
• Intracellular Signaling Peptides and Proteins
• Neuropeptides
• Orexins
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Antigen Presentation (genetics, immunology)
• Autoimmune Diseases (genetics, immunology, metabolism)
• Genetic Association Studies
• HLA Antigens (genetics, immunology)
• Humans
• Intracellular Signaling Peptides and Proteins (genetics, immunology, metabolism)
• Narcolepsy (genetics, immunology, physiopathology)
• Neuropeptides (genetics, immunology, metabolism)
• Orexins
• Receptors, Antigen, T-Cell, alpha-beta (genetics, metabolism)
• White People