ImmunoChip study implicates antigen presentation to T cells in narcolepsy

PLoS Genet. 2013;9(2):e1003270. doi: 10.1371/journal.pgen.1003270. Epub 2013 Feb 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation* / genetics
  • Antigen Presentation* / immunology
  • Autoimmune Diseases* / genetics
  • Autoimmune Diseases* / immunology
  • Autoimmune Diseases* / metabolism
  • European Continental Ancestry Group
  • Genetic Association Studies
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Narcolepsy / genetics*
  • Narcolepsy / immunology
  • Narcolepsy / physiopathology
  • Neuropeptides / genetics
  • Neuropeptides / immunology
  • Neuropeptides / metabolism
  • Orexins
  • Receptors, Antigen, T-Cell, alpha-beta* / genetics
  • Receptors, Antigen, T-Cell, alpha-beta* / metabolism

Substances

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