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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 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.


Vyšlo v časopise: ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy. PLoS Genet 9(2): e32767. doi:10.1371/journal.pgen.1003270
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003270

Souhrn

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.


Zdroje

1. MignotE (1998) Genetic and familial aspects of narcolepsy. Neurology 50: S16–22.

2. HanF, LinL, WarbySC, FaracoJ, LiJ, et al. (2011) Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China. Annals of neurology 70: 410–417.

3. PartinenM, Saarenpaa-HeikkilaO, IlveskoskiI, HublinC, LinnaM, et al. (2012) Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PLoS ONE 7: e33723 doi:10.1371/journal.pone.0033723.

4. LongstrethWTJr, TonTG, KoepsellTD (2009) Narcolepsy and streptococcal infections. Sleep 32: 1548.

5. AranA, EinenM, LinL, PlazziG, NishinoS, et al. (2010) Clinical and therapeutic aspects of childhood narcolepsy-cataplexy: a retrospective study of 51 children. Sleep 33: 1457–1464.

6. HongSC, LinL, LoB, JeongJH, ShinYK, et al. (2007) DQB1*0301 and DQB1*0601 modulate narcolepsy susceptibility in Koreans. Human immunology 68: 59–68.

7. HorH, KutalikZ, DauvilliersY, ValsesiaA, LammersGJ, et al. (2010) Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. Nature genetics 42: 786–789.

8. HanF, LinL, LiJ, DongSX, AnP, et al. (2012) HLA-DQ association and allele competition in Chinese narcolepsy. Tissue Antigens 80: 328–335.

9. WinkelmannJ, LinL, SchormairB, KornumBR, FaracoJ, et al. (2012) Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. Human molecular genetics 21: 2205–2210.

10. RamosPS, CriswellLA, MoserKL, ComeauME, WilliamsAH, et al. (2011) A comprehensive analysis of shared loci between systemic lupus erythematosus (SLE) and sixteen autoimmune diseases reveals limited genetic overlap. PLoS Genet 7: e1002406 doi:10.1371/journal.pgen.1002406.

11. Gutierrez-AchuryJ, Coutinho de AlmeidaR, WijmengaC (2011) Shared genetics in coeliac disease and other immune-mediated diseases. Journal of internal medicine 269: 591–603.

12. HallmayerJ, FaracoJ, LinL, HesselsonS, WinkelmannJ, et al. (2009) Narcolepsy is strongly associated with the T-cell receptor alpha locus. Nature genetics 41: 708–711.

13. MiyagawaT, HondaM, KawashimaM, ShimadaM, TanakaS, et al. (2010) Polymorphism located in TCRA locus confers susceptibility to essential hypersomnia with HLA-DRB1*1501-DQB1*0602 haplotype. Journal of human genetics 55: 63–65.

14. CooperJD, SmythDJ, SmilesAM, PlagnolV, WalkerNM, et al. (2008) Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. Nature genetics 40: 1399–1401.

15. BarrettJC, ClaytonDG, ConcannonP, AkolkarB, CooperJD, et al. (2009) Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature genetics 41: 703–707.

16. TorikaiH, AkatsukaY, MiyazakiM, TsujimuraA, YatabeY, et al. (2006) The human cathepsin H gene encodes two novel minor histocompatibility antigen epitopes restricted by HLA-A*3101 and -A*3303. British journal of haematology 134: 406–416.

17. ConusS, SimonHU (2010) Cathepsins and their involvement in immune responses. Swiss medical weekly 140: w13042.

18. ColbertJD, MatthewsSP, MillerG, WattsC (2009) Diverse regulatory roles for lysosomal proteases in the immune response. European journal of immunology 39: 2955–2965.

19. BuhlingF, KouadioM, ChwieralskiCE, KernU, HohlfeldJM, et al. (2011) Gene targeting of the cysteine peptidase cathepsin H impairs lung surfactant in mice. PLoS ONE 6: e26247 doi:10.1371/journal.pone.0026247.

20. LiX, WuK, EdmanM, Schenke-LaylandK, MacVeigh-AloniM, et al. (2010) Increased expression of cathepsins and obesity-induced proinflammatory cytokines in lacrimal glands of male NOD mouse. Investigative ophthalmology & visual science 51: 5019–5029.

21. Cunninghame GrahamDS, GrahamRR, MankuH, WongAK, WhittakerJC, et al. (2008) Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosus. Nature genetics 40: 83–89.

22. GourhP, ArnettFC, TanFK, AssassiS, DivechaD, et al. (2010) Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis. Annals of the rheumatic diseases 69: 550–555.

23. Bossini-CastilloL, BroenJC, SimeonCP, BerettaL, VonkMC, et al. (2011) A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort. Annals of the rheumatic diseases 70: 638–641.

24. IshiiN, TakahashiT, SorooshP, SugamuraK (2010) OX40-OX40 ligand interaction in T-cell-mediated immunity and immunopathology. Advances in immunology 105: 63–98.

25. GoughMJ, WeinbergAD (2009) OX40 (CD134) and OX40L. Advances in experimental medicine and biology 647: 94–107.

26. HirotaT, TakahashiA, KuboM, TsunodaT, TomitaK, et al. (2012) Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nature genetics

27. WatermanM, XuW, StempakJM, MilgromR, BernsteinCN, et al. (2011) Distinct and overlapping genetic loci in Crohn's disease and ulcerative colitis: correlations with pathogenesis. Inflammatory bowel diseases 17: 1936–1942.

28. LindstromS, VachonCM, LiJ, VargheseJ, ThompsonD, et al. (2011) Common variants in ZNF365 are associated with both mammographic density and breast cancer risk. Nature genetics 43: 185–187.

29. KangHM, SulJH, ServiceSK, ZaitlenNA, KongSY, et al. (2010) Variance component model to account for sample structure in genome-wide association studies. Nature genetics 42: 348–354.

30. ThompsonSD, SudmanM, RamosPS, MarionMC, RyanM, et al. (2010) The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1. Arthritis and rheumatism 62: 3265–3276.

31. PurcellS, NealeB, Todd-BrownK, ThomasL, FerreiraMA, et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. American journal of human genetics 81: 559–575.

32. BarrettJC, FryB, MallerJ, DalyMJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21: 263–265.

33. ClarkeL, Zheng-BradleyX, SmithR, KuleshaE, XiaoC, et al. (2012) The 1000 Genomes Project: data management and community access. Nature methods 9: 459–462.

34. BrowningSR, BrowningBL (2007) Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. American journal of human genetics 81: 1084–1097.

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Genetika Reprodukčná medicína

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