Tafti, Mehdi and Lammers, Gert J. and Dauvilliers, Yves and Overeem, Sebastiaan and Mayer, Geert and Nowak, Jacek and Pfister, Corinne and Dubois, Valerie and Eliaou, Jean-Francois and Eberhard, Hans-Peter and Liblau, Roland and Wierzbicka, Aleksandra and Geisler, Peter and Bassetti, Claudio L. and Mathis, Johannes and Lecendreux, Michel and Khatami, Ramin and Heinzer, Raphael and Haba-Rubio, Jose and Feketeova, Eva and Baumann, Christian R. and Kutalik, Zoltan and Tiercy, Jean-Marie (2016) Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity. SLEEP, 39 (3): PII sp-003. pp. 581-587. ISSN 0161-8105, 1550-9109
Full text not available from this repository. (Request a copy)Abstract
Study Objectives: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells. Methods: HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4,043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles. Results: HLA-A*11:01 (OR = 1.49 [1.18-1.87] P = 7.0*10(-4)), C* 04: 01 (OR = 1.34 [1.10-1.63] P = 3.23*10(-3)), and B*35:01 (OR = 1.46 [1.13-1.89] P = 3.64*10(-3)) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr(9) (OR = 1.32 [1.15-1.52] P = 6.95*10(-5)) and HLA-C-Ser11 (OR = 1.34 [1.15-1.57] P = 2.43*10(-4)). Conclusions: Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; MULTIPLE-SCLEROSIS; CATAPLEXY; PEPTIDES; ANTIGENS; RISK; POPULATION; HAPLOTYPES; PROTECTION; COMPLEX; autoimmunity; hypocretin/orexin; CD4; CD8; cytotoxicity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Mar 2019 10:31 |
| Last Modified: | 12 Mar 2019 10:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2342 |
Actions (login required)
 |
View Item |
