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

doi:10.1371/journal.pgen.1003270

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 KemlinkKarel 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

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193 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	P L o S Genetics
Vol/bind	9
Udgave nummer	2
Sider (fra-til)	e1003270
ISSN	1553-7404
DOI	https://doi.org/10.1371/journal.pgen.1003270
Status	Udgivet - 2013

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10.1371/journal.pgen.1003270

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Faraco, J., Lin, L., Kornum, B. R., Kenny, E. E., Trynka, G., Einen, M., Rico, T. J., Lichtner, P., Dauvilliers, Y., Arnulf, I., Lecendreux, M., Javidi, S., Geisler, P., Mayer, G., Pizza, F., Poli, F., Plazzi, G., Overeem, S., Lammers, G. J., ... Mignot, E. (2013). ImmunoChip study implicates antigen presentation to T cells in narcolepsy. P L o S Genetics, 9(2), e1003270. https://doi.org/10.1371/journal.pgen.1003270

Faraco, J, Lin, L, Kornum, BR, Kenny, EE, Trynka, G, Einen, M, Rico, TJ, Lichtner, P, Dauvilliers, Y, Arnulf, I, Lecendreux, M, Javidi, S, Geisler, P, Mayer, G, Pizza, F, Poli, F, Plazzi, G, Overeem, S, Lammers, GJ, Kemlink, D, Sonka, K, Nevsimalova, S, Rouleau, G, Desautels, A, Montplaisir, J, Frauscher, B, Ehrmann, L, Högl, B, Jennum, P, Bourgin, P, Peraita-Adrados, R, Iranzo, A, Bassetti, C, Chen, W-M, Concannon, P, Thompson, SD, Damotte, V, Fontaine, B, Breban, M, Gieger, C, Klopp, N, Deloukas, P, Wijmenga, C, Hallmayer, J, Onengut-Gumuscu, S, Rich, SS, Winkelmann, J & Mignot, E 2013, 'ImmunoChip study implicates antigen presentation to T cells in narcolepsy', P L o S Genetics, bind 9, nr. 2, s. e1003270. https://doi.org/10.1371/journal.pgen.1003270

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title = "ImmunoChip study implicates antigen presentation to T cells in narcolepsy",

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.",

keywords = "Antigen Presentation, Autoimmune Diseases, European Continental Ancestry Group, Genetic Association Studies, HLA Antigens, Humans, Intracellular Signaling Peptides and Proteins, Narcolepsy, Neuropeptides, Receptors, Antigen, T-Cell, alpha-beta",

author = "Juliette Faraco and Ling Lin and Kornum, {Birgitte Rahbek} and Kenny, {Eimear E} and Gosia Trynka and Mali Einen and Rico, {Tom J} and Peter Lichtner and Yves Dauvilliers and Isabelle Arnulf and Michel Lecendreux and Sirous Javidi and Peter Geisler and Geert Mayer and Fabio Pizza and Francesca Poli and Giuseppe Plazzi and Sebastiaan Overeem and Lammers, {Gert Jan} and David Kemlink and Karel Sonka and Sona Nevsimalova and Guy Rouleau and Alex Desautels and Jacques Montplaisir and Birgit Frauscher and Laura Ehrmann and Birgit H{\"o}gl and Poul Jennum and Patrice Bourgin and Rosa Peraita-Adrados and Alex Iranzo and Claudio Bassetti and Wei-Min Chen and Patrick Concannon and Thompson, {Susan D} and Vincent Damotte and Bertrand Fontaine and Maxime Breban and Christian Gieger and Norman Klopp and Panos Deloukas and Cisca Wijmenga and Joachim Hallmayer and Suna Onengut-Gumuscu and Rich, {Stephen S} and Juliane Winkelmann and Emmanuel Mignot",

year = "2013",

doi = "10.1371/journal.pgen.1003270",

language = "English",

volume = "9",

pages = "e1003270",

journal = "P L o S Genetics",

issn = "1553-7404",

publisher = "Public Library of Science",

number = "2",

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TY - JOUR

T1 - ImmunoChip study implicates antigen presentation to T cells in narcolepsy

AU - Faraco, Juliette

AU - Lin, Ling

AU - Kornum, Birgitte Rahbek

AU - Kenny, Eimear E

AU - Trynka, Gosia

AU - Einen, Mali

AU - Rico, Tom J

AU - Lichtner, Peter

AU - Dauvilliers, Yves

AU - Arnulf, Isabelle

AU - Lecendreux, Michel

AU - Javidi, Sirous

AU - Geisler, Peter

AU - Mayer, Geert

AU - Pizza, Fabio

AU - Poli, Francesca

AU - Plazzi, Giuseppe

AU - Overeem, Sebastiaan

AU - Lammers, Gert Jan

AU - Kemlink, David

AU - Sonka, Karel

AU - Nevsimalova, Sona

AU - Rouleau, Guy

AU - Desautels, Alex

AU - Montplaisir, Jacques

AU - Frauscher, Birgit

AU - Ehrmann, Laura

AU - Högl, Birgit

AU - Jennum, Poul

AU - Bourgin, Patrice

AU - Peraita-Adrados, Rosa

AU - Iranzo, Alex

AU - Bassetti, Claudio

AU - Chen, Wei-Min

AU - Concannon, Patrick

AU - Thompson, Susan D

AU - Damotte, Vincent

AU - Fontaine, Bertrand

AU - Breban, Maxime

AU - Gieger, Christian

AU - Klopp, Norman

AU - Deloukas, Panos

AU - Wijmenga, Cisca

AU - Hallmayer, Joachim

AU - Onengut-Gumuscu, Suna

AU - Rich, Stephen S

AU - Winkelmann, Juliane

AU - Mignot, Emmanuel

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Antigen Presentation

KW - Autoimmune Diseases

KW - European Continental Ancestry Group

KW - Genetic Association Studies

KW - HLA Antigens

KW - Humans

KW - Intracellular Signaling Peptides and Proteins

KW - Narcolepsy

KW - Neuropeptides

KW - Receptors, Antigen, T-Cell, alpha-beta

U2 - 10.1371/journal.pgen.1003270

DO - 10.1371/journal.pgen.1003270

M3 - Journal article

C2 - 23459209

SN - 1553-7404

VL - 9

SP - e1003270

JO - P L o S Genetics

JF - P L o S Genetics

IS - 2

ER -

ImmunoChip study implicates antigen presentation to T cells in narcolepsy

Abstract

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