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...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	PLoS genetics Ročník 9; číslo 2; s. e1003270
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 01.02.2013 Public Library of Science (PLoS)
Témata:	Antigen Presentation - genetics Antigen Presentation - immunology Antigens Autoimmune diseases Autoimmune Diseases - genetics Autoimmune Diseases - immunology Autoimmune Diseases - metabolism Biochemistry, Molecular Biology Biology Confidence intervals Disease Disease susceptibility European Continental Ancestry Group Gene expression Genealogy Genetic aspects Genetic Association Studies Genetics Genomes Grants Haplotypes Health aspects Health sciences 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 Life Sciences Lymphocytes Narcolepsy Narcolepsy - genetics Narcolepsy - immunology Narcolepsy - physiopathology Neuropeptides - genetics Neuropeptides - immunology Neuropeptides - metabolism Orexins Physiological aspects Principal components analysis Receptors, Antigen, T-Cell, alpha-beta - genetics Receptors, Antigen, T-Cell, alpha-beta - metabolism Sleep disorders T cell receptors T cells Netherlands Haplotypes Cytokines Europe Genetic loci T cell receptors Narcolepsy Autoimmune diseases T cells
ISSN:	1553-7404, 1553-7390, 1553-7404
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: J Faraco, L Lin, P Deloukas, J Hallmayer, SS Rich, E Mignot. Performed the experiments: J Faraco, L Lin, BR Kornum, G Trynka, TJ Rico, P Lichtner, W-M Chen, S Onengut-Gumuscu, SS Rich, J Winkelmann P Concannon. Analyzed the data: J Faraco, L Lin, J Hallmayer, EE Kenny, BR Kornum, E Mignot. Contributed reagents/materials/analysis tools: A Desautels, A Iranzo, B Frauscher, B Fontaine, B Högl, C Bassetti, C Gieger, C Wijmenga, D Kemlink, EE Kenny, E Mignot, F Pizza, F Poli, GJ Lammer, G Mayer, G Plazzi, G Rouleau, G Trynka, I Arnulf, J Montplaisir, J Winkelmann, K Sonka, L Ehrmann, M Breban, M Einen, M Lecendreux, N Klopp, P Bourgin, P Concannon, P Deloukas, P Geisler, P Jennum, P Lichtner, R Peraita-Adrados, S Javidi, S Nevsimalova, S Overeem, S Onengut-Gumuscu, SS Rich, SD Thompson, TJ Rico, V Damotte, W-M Chen, Y Dauvilliers, J Hallmayer. Wrote the paper: J Faraco, J Hallmayer, EE Kenny, SS Rich, P Deloukas, J Winkelmann, E Mignot. The authors have declared that no competing interests exist.
ISSN:	1553-7404 1553-7390 1553-7404
DOI:	10.1371/journal.pgen.1003270