ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Faraco, Juliette, Lin, Ling, Kornum, Birgitte Rahbek, Kenny, Eimear E., Trynka, Gosia, Einen, Mali, Rico, Tom J., Lichtner, Peter, Dauvilliers, Yves, Arnulf, Isabelle, Lecendreux, Michel, Javidi, Sirous, Geisler, Peter, Mayer, Geert, Pizza, Fabio, Poli, Francesca, Plazzi, Giuseppe, Overeem, Sebastiaan, Lammers, Gert Jan, Kemlink, David, Sonka, Karel, Nevsimalova, Sona, Rouleau, Guy, Desautels, Alex, Montplaisir, Jacques, Frauscher, Birgit, Ehrmann, Laura, Högl, Birgit, Jennum, Poul, Bourgin, Patrice, Peraita-Adrados, Rosa, Iranzo, Alex, Bassetti, Claudio, Chen, Wei-Min, Concannon, Patrick, Thompson, Susan D., Damotte, Vincent, Fontaine, Bertrand, Breban, Maxime, Gieger, Christian, Klopp, Norman, Deloukas, Panos, Wijmenga, Cisca, Hallmayer, Joachim, Onengut-Gumuscu, Suna, Rich, Stephen S., Winkelmann, Juliane, Mignot, Emmanuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573113/
https://www.ncbi.nlm.nih.gov/pubmed/23459209
http://dx.doi.org/10.1371/journal.pgen.1003270
Descripción
Sumario: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.

Ejemplares similares