PLoS Genetics (Jan 2013)
ImmunoChip study implicates antigen presentation to T cells in narcolepsy.
- 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
Affiliations
- 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
- DOI
- https://doi.org/10.1371/journal.pgen.1003270
- Journal volume & issue
-
Vol. 9,
no. 2
p. e1003270
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.
