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. Kemlink; K. 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

doi:10.1371/journal.pgen.1003270

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

Research output: Contribution to journal › Article › Academic › peer-review

154 Citations (Scopus)

49 Downloads (Pure)

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 language	English
Article number	e1003270
Pages (from-to)	1-7
Journal	PLoS Genetics
Volume	9
Issue number	2
DOIs	https://doi.org/10.1371/journal.pgen.1003270
Publication status	Published - Feb 2013
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1371/journal.pgen.1003270

immunoFinal published version, 746 KB

Cite this

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. PLoS Genetics, 9(2), 1-7. [e1003270]. https://doi.org/10.1371/journal.pgen.1003270

@article{93ad186108ab43eca7ff3bf9a6012466,

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. {\textcopyright} 2013 Faraco et al.",

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",

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

year = "2013",

month = feb,

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

language = "English",

volume = "9",

pages = "1--7",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "2",

}

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, CL, Chen, WM, 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', PLoS Genetics, vol. 9, no. 2, e1003270, pp. 1-7. https://doi.org/10.1371/journal.pgen.1003270

TY - JOUR

T1 - ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

AU - Faraco, J.

AU - Lin, L.

AU - Kornum, B.R.

AU - Kenny, E.E.

AU - Trynka, G.

AU - Einen, M.

AU - Rico, T.J.

AU - Lichtner, P.

AU - Dauvilliers, Y.

AU - Arnulf, I.

AU - Lecendreux, M.

AU - Javidi, S.

AU - Geisler, P.

AU - Mayer, G.

AU - Pizza, F.

AU - Poli, F.

AU - Plazzi, G.

AU - Overeem, S.

AU - Lammers, G.J.

AU - Kemlink, D.

AU - Sonka, K.

AU - Nevsimalova, S.

AU - Rouleau, G.

AU - Desautels, A.

AU - Montplaisir, J.

AU - Frauscher, B.

AU - Ehrmann, L.

AU - Högl, B.

AU - Jennum, P.

AU - Bourgin, P.

AU - Peraita-Adrados, R.

AU - Iranzo, A.

AU - Bassetti, C.L.

AU - Chen, W.M.

AU - Concannon, P.

AU - Thompson, S.D.

AU - Damotte, V.

AU - Fontaine, B.

AU - Breban, M.

AU - Gieger, C.

AU - Klopp, N.

AU - Deloukas, P.

AU - Wijmenga, C.

AU - Hallmayer, J.

AU - Onengut-Gumuscu, S.

AU - Rich, S.S.

AU - Winkelmann, J.

AU - Mignot, E.

PY - 2013/2

Y1 - 2013/2

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. © 2013 Faraco et al.

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. © 2013 Faraco et al.

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 - Orexins

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

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

UR - http://www.scopus.com/inward/record.url?scp=84874783317&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1003270

DO - 10.1371/journal.pgen.1003270

M3 - Article

C2 - 23459209

VL - 9

SP - 1

EP - 7

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 2

M1 - e1003270

ER -

ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this