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.
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; Pizza, Fabio; Poli, Francesca; Plazzi, Giuseppe; 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., Bassetti; W., 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. - In: PLOS GENETICS. - ISSN 1553-7390. - 9:2(2013), pp. 1-7. [10.1371/journal.pgen.1003270]
ImmunoChip study implicates antigen presentation to T cells in narcolepsy
PLAZZI, GIUSEPPE;
2013
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.
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