ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

J. Faraco, L. Lin, B.R. Kornum, E.E. Kenny, G. Trynka, M. Einen, T.J. Rico, P. Lichtner, Y. Dauvilliers, I. Arnulf, M. Lecendreux, S. Javidi, P. Geisler, G. Mayer, F. Pizza, F. Poli, G. Plazzi, S. Overeem, G.J. Lammers, D. KemlinkK. Sonka, S. Nevsimalova, G. Rouleau, A. Desautels, J. Montplaisir, B. Frauscher, L. Ehrmann, B. Högl, P. Jennum, P. Bourgin, R. Peraita-Adrados, A. Iranzo, C.L. Bassetti, W.M. Chen, P. Concannon, S.D. Thompson, V. Damotte, B. Fontaine, M. Breban, C. Gieger, N. Klopp, P. Deloukas, C. Wijmenga, J. Hallmayer, S. Onengut-Gumuscu, S.S. Rich, J. Winkelmann, E. Mignot

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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. © 2013 Faraco et al.

Original languageEnglish
Article numbere1003270
Pages (from-to)1-7
JournalPLoS Genetics
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 2013
Externally publishedYes

Keywords

  • Antigen Presentation
  • Autoimmune Diseases
  • European Continental Ancestry Group
  • Genetic Association Studies
  • HLA Antigens
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Narcolepsy
  • Neuropeptides
  • Orexins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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