Genetic Factors in Neuroimmune Diseases

  • Alessandro DidonnaEmail author
  • Ester Cantó
Part of the Contemporary Clinical Neuroscience book series (CCNE)


Neuroimmune diseases consist of a heterogeneous group of neurological disorders characterized by aberrant immune responses against either the central or the peripheral nervous system. Unlike monogenic diseases, neuroimmune disorders do not follow Mendelian patterns of inheritance, and their genetic basis has been elusive for decades. It has been only recently that novel methodologies of analysis, such as the genome-wide association study (GWAS) paradigm, have provided the tools for deciphering the complex genetic architecture proper of these disorders. Indeed, immunogenetic and epidemiological data suggest a polygenic model of inheritance in which the interplay between multiple genetic and environmental factors is crucial for disease risk. Among the different genetic determinants, the major histocompatibility complex (MHC) locus accounts for the highest component of genetic risk for the vast majority of neuroimmune disorders, suggesting that dysfunctions in the antigen presentation process likely play a pivotal role in their pathophysiology. However, further studies will be necessary to fully describe the multifactorial nature of such complex diseases and discover all the molecular pathways associated with the different risk variants.


Neuroimmune diseases Major histocompatibility complex (MHC) Human leukocyte antigen (HLA) Genome-wide association study (GWAS) Autoimmunity 



AD holds a Marilyn Hilton Award for Innovation in MS Research from the Conrad N. Hilton Foundation (#17323). The work was also supported by FISM-Fondazione Italiana Sclerosi Multipla Senior Research Fellowships Cod. 2014/B/1 and Cod. 2017/B/3 to AD and financed or co-financed with the “5 per mille” public funding.


  1. 1.
    Wells E, Hacohen Y, Waldman A, Tillema JM, Soldatos A, Ances B, Benseler S, Bielekova B, Dale RC, Dalmau J, Gaillard W, Gorman M, Greenberg B, Hyslop A, Pardo CA, Tasker RC, Yeh EA, Bar-Or A, Pittock S, Vanderver A, Banwell B. Neuroimmune disorders of the central nervous system in children in the molecular era. Nat Rev Neurol. 2018;14(7):433–45. Scholar
  2. 2.
    Schork NJ, Murray SS, Frazer KA, Topol EJ. Common vs. rare allele hypotheses for complex diseases. Curr Opin Genet Dev. 2009;19(3):212–9. Scholar
  3. 3.
    Pulst SM. Genetic linkage analysis. Arch Neurol. 1999;56(6):667–72.PubMedCrossRefGoogle Scholar
  4. 4.
    Botstein D, White RL, Skolnick M, Davis RW. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 1980;32(3):314–31.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Olson M, Hood L, Cantor C, Botstein D. A common language for physical mapping of the human genome. Science. 1989;245(4925):1434–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Hearne CM, Ghosh S, Todd JA. Microsatellites for linkage analysis of genetic traits. Trends Genet. 1992;8(8):288–94.PubMedCrossRefGoogle Scholar
  7. 7.
    Bush WS, Moore JH. Chapter 11: Genome-wide association studies. PLoS Comput Biol. 2012;8(12):e1002822. Scholar
  8. 8.
    Manolio TA. Genomewide association studies and assessment of the risk of disease. N Engl J Med. 2010;363(2):166–76. Scholar
  9. 9.
    Hirschhorn JN, Daly MJ. Genome-wide association studies for common diseases and complex traits. Nat Rev Genet. 2005;6(2):95–108. Scholar
  10. 10.
    Slatkin M. Linkage disequilibrium--understanding the evolutionary past and mapping the medical future. Nat Rev Genet. 2008;9(6):477–85. Scholar
  11. 11.
    Metzker ML. Sequencing technologies – the next generation. Nat Rev Genet. 2010;11(1):31–46. Scholar
  12. 12.
    Horton R, Wilming L, Rand V, Lovering RC, Bruford EA, Khodiyar VK, Lush MJ, Povey S, Talbot CC Jr, Wright MW, Wain HM, Trowsdale J, Ziegler A, Beck S. Gene map of the extended human MHC. Nat Rev Genet. 2004;5(12):889–99. Scholar
  13. 13.
    Kulski JK, Shiina T, Anzai T, Kohara S, Inoko H. Comparative genomic analysis of the MHC: the evolution of class I duplication blocks, diversity and complexity from shark to man. Immunol Rev. 2002;190:95–122.PubMedCrossRefGoogle Scholar
  14. 14.
    Ting JP, Trowsdale J. Genetic control of MHC class II expression. Cell. 2002;(109 Suppl):S21–33.PubMedCrossRefGoogle Scholar
  15. 15.
    Milner CM, Campbell RD. Genetic organization of the human MHC class III region. Front Biosci. 2001;6:D914–26.PubMedCrossRefGoogle Scholar
  16. 16.
    Hauser SL, Goodin DS. Multiple sclerosis and other demyelinating diseases. In: Harrison’s principle of internal medicine., 18th Edition. New York: McGraw-Hill; 2012.Google Scholar
  17. 17.
    Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502–17. Scholar
  18. 18.
    Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurol Sci. 2001;22(2):117–39.PubMedCrossRefGoogle Scholar
  19. 19.
    Koch M, Kingwell E, Rieckmann P, Tremlett H. The natural history of primary progressive multiple sclerosis. Neurology. 2009;73(23):1996–2002. Scholar
  20. 20.
    Sadovnick AD, Baird PA. The familial nature of multiple sclerosis: age-corrected empiric recurrence risks for children and siblings of patients. Neurology. 1988;38(6):990–1.PubMedCrossRefGoogle Scholar
  21. 21.
    Willer CJ, Dyment DA, Risch NJ, Sadovnick AD, Ebers GC, Canadian Collaborative Study Group. Twin concordance and sibling recurrence rates in multiple sclerosis. Proc Natl Acad Sci U S A. 2003;100(22):12877–82. Scholar
  22. 22.
    Robertson NP, Fraser M, Deans J, Clayton D, Walker N, Compston DA. Age-adjusted recurrence risks for relatives of patients with multiple sclerosis. Brain. 1996;119(Pt 2):449–55.PubMedCrossRefGoogle Scholar
  23. 23.
    Naito S, Namerow N, Mickey MR, Terasaki PI. Multiple sclerosis: association with HL-A3. Tissue Antigens. 1972;2(1):1–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Jersild C, Svejgaard A, Fog T. HL-A antigens and multiple sclerosis. Lancet. 1972;1(7762):1240–1.PubMedCrossRefGoogle Scholar
  25. 25.
    Haines JL, Terwedow HA, Burgess K, Pericak-Vance MA, Rimmler JB, Martin ER, Oksenberg JR, Lincoln R, Zhang DY, Banatao DR, Gatto N, Goodkin DE, Hauser SL. Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group. Hum Mol Genet. 1998;7(8):1229–34.PubMedCrossRefGoogle Scholar
  26. 26.
    International Multiple Sclerosis Genetics Consortium (IMSGC), Wellcome Trust Case Control Consortium 2 (WTCCC2). Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476(7359):214–9. Scholar
  27. 27.
    Patsopoulos NA, Barcellos LF, Hintzen RQ, Schaefer C, van Duijn CM, Noble JA, Raj T, Imsgc A, Gourraud PA, Stranger BE, Oksenberg J, Olsson T, Taylor BV, Sawcer S, Hafler DA, Carrington M, De Jager PL, de Bakker PI. Fine-mapping the genetic association of the major histocompatibility complex in multiple sclerosis: HLA and non-HLA effects. PLoS Genet. 2013;9(11):e1003926. Scholar
  28. 28.
    Moutsianas L, Jostins L, Beecham AH, Dilthey AT, Xifara DK, Ban M, Shah TS, Patsopoulos NA, Alfredsson L, Anderson CA, Attfield KE, Baranzini SE, Barrett J, Binder TM, Booth D, Buck D, Celius EG, Cotsapas C, D’Alfonso S, Dendrou CA, Donnelly P, Dubois B, Fontaine B, Lar Fugger L, Goris A, Gourraud PA, Graetz C, Hemmer B, Hillert J, International IBDGC, Kockum I, Leslie S, Lill CM, Martinelli-Boneschi F, Oksenberg JR, Olsson T, Oturai A, Saarela J, Sondergaard HB, Spurkland A, Taylor B, Winkelmann J, Zipp F, Haines JL, Pericak-Vance MA, Spencer CC, Stewart G, Hafler DA, Ivinson AJ, Harbo HF, Hauser SL, De Jager PL, Compston A, McCauley JL, Sawcer S, McVean G, International Multiple Sclerosis Genetics Consortium (IMSGC). Class II HLA interactions modulate genetic risk for multiple sclerosis. Nat Genet. 2015;47(10):1107–13. Scholar
  29. 29.
    Patsopoulos N, Baranzini SE, Santaniello A, Shoostari P, Cotsapas C, Wong G, Beecham AH, James T, Replogle J, Vlachos I, McCabe C, Pers T, Brandes A, White C, Keenan B, Cimpean M, Winn P, Panteliadis I-P, Robbins A, Andlauer TFM, Zarzycki O, Dubois B, Goris A, Bach Sondergaard H, Sellebjerg F, Soelberg Sorensen P, Ullum H, Wegner Thoerner L, Saarela J, Cournu-Rebeix I, Damotte V, Fontaine B, Guillot-Noel L, Lathrop M, Vukusik S, Berthele A, Biberacher V, Buck D, Gasperi C, Graetz C, Grummel V, Hemmer B, Hoshi M, Knier B, Korn T, Lill CM, Luessi F, Muhlau M, Zipp F, Dardiotis E, Agliardi C, Amoroso A, Barizzone N, Benedetti MD, Bernardinelli L, Cavalla P, Clarelli F, Comi G, Cusi D, Esposito F, Ferre L, Galimberti D, Guaschino C, Leone MA, Martinelli V, Moiola L, Salvetti M, Sorosina M, Vecchio D, Zauli A, Santoro S, Zuccala M, Mescheriakova J, van Duijn C, Bos SD, Celius EG, Spurkland A, Comabella M, Montalban X, Alfredsson L, Bomfim IL, Gomez-Cabrero D, Hillert J, Jagodic M, Linden M, Piehl F, Jelcic I, Martin R, Sospedra M, Baker A, Ban M, Hawkins C, Hysi P, Kalra S, Karpe F, Khadake J, Lachance G, Molyneux P, Neville M, Thorpe J, Bradshaw E, Caillier SJ, Calabresi P, Cree BAC, Cross A, Davis MF, de Bakker P, Delgado S, Dembele M, Edwards K, Fitzgerald K, Frohlich IY, Gourraud P-A, Haines JL, Hakonarson H, Kimbrough D, Isobe N, Konidari I, Lathi E, Lee MH, Li T, An D, Zimmer A, Lo A, Madireddy L, Manrique CP, Mitrovic M, Olah M, Patrick E, Pericak-Vance MA, Piccio L, Schaefer C, Weiner H, Lage K, Compston A, Hafler D, Harbo HF, Hauser SL, Stewart G, D’Alfonso S, Hadjigeorgiou G, Taylor B, Barcellos LF, Booth D, Hintzen R, Kockum I, Martinelli-Boneschi F, McCauley JL, Oksenberg JR, Oturai A, Sawcer S, Ivinson AJ, Olsson T, De Jager PL. The Multiple Sclerosis Genomic Map: role of peripheral immune cells and resident microglia in susceptibility. bioRxiv. 2017;
  30. 30.
    McElroy JP, Isobe N, Gourraud PA, Caillier SJ, Matsushita T, Kohriyama T, Miyamoto K, Nakatsuji Y, Miki T, Hauser SL, Oksenberg JR, Kira J. SNP-based analysis of the HLA locus in Japanese multiple sclerosis patients. Genes Immun. 2011;12(7):523–30. Scholar
  31. 31.
    Qiu W, James I, Carroll WM, Mastaglia FL, Kermode AG. HLA-DR allele polymorphism and multiple sclerosis in Chinese populations: a meta-analysis. Mult Scler. 2011;17(4):382–8. Scholar
  32. 32.
    Isobe N, Matsushita T, Yamasaki R, Ramagopalan SV, Kawano Y, Nishimura Y, Ebers GC, Kira J. Influence of HLA-DRB1 alleles on the susceptibility and resistance to multiple sclerosis in Japanese patients with respect to anti-aquaporin 4 antibody status. Mult Scler. 2010;16(2):147–55. Scholar
  33. 33.
    Yoshimura S, Isobe N, Yonekawa T, Matsushita T, Masaki K, Sato S, Kawano Y, Yamamoto K, Kira J, South Japan Multiple Sclerosis Genetics Consortium. Genetic and infectious profiles of Japanese multiple sclerosis patients. PLoS One. 2012;7(11):e48592. Scholar
  34. 34.
    Oksenberg JR, Barcellos LF, Cree BA, Baranzini SE, Bugawan TL, Khan O, Lincoln RR, Swerdlin A, Mignot E, Lin L, Goodin D, Erlich HA, Schmidt S, Thomson G, Reich DE, Pericak-Vance MA, Haines JL, Hauser SL. Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans. Am J Hum Genet. 2004;74(1):160–7. Scholar
  35. 35.
    Isobe N, Gourraud PA, Harbo HF, Caillier SJ, Santaniello A, Khankhanian P, Maiers M, Spellman S, Cereb N, Yang S, Pando MJ, Piccio L, Cross AH, De Jager PL, Cree BA, Hauser SL, Oksenberg JR. Genetic risk variants in African Americans with multiple sclerosis. Neurology. 2013;81(3):219–27. Scholar
  36. 36.
    International Multiple Sclerosis Genetics Consortium (IMSGC), Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, de Bakker PI, Gabriel SB, Mirel DB, Ivinson AJ, Pericak-Vance MA, Gregory SG, Rioux JD, McCauley JL, Haines JL, Barcellos LF, Cree B, Oksenberg JR, Hauser SL. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med. 2007;357(9):851–62. Scholar
  37. 37.
    International Multiple Sclerosis Genetics Consortium (IMSGC). Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45(11):1353–60. Scholar
  38. 38.
    Mitrovic M, Patsopoulos N, Beecham A, Dankowski T, Goris A, Dubois B, Dhooghe M-B, Lemmens R, Van Damme P, Fitzgerald K, Bach Sondergaard H, Sellebjerg F, Sorensen PS, Ullum H, Wegner Thoerner L, Werge T, Saarela J, Cournu-Rebeix I, Damotte V, Fontaine B, Guillot-Noel L, Lathrop M, Vukusik S, Gourraud P-A, Andlauer T, Pongratz V, Buck D, Gasperi C, Graetz C, Bayas A, Heesen C, Kumpfel T, Linker R, Paul F, Stangel M, Tackenberg B, Then Bergh F, Warnke C, Wiendl H, Wildemann B, Zettl U, Ziemann U, Tumani H, Gold R, Grummel V, Hemmer B, Knier B, Lill C, Luessi E, Dardiotis E, Agliardi C, Barizzone N, Mascia E, Bernardinelli L, Comi G, Cusi D, Esposito F, Ferre L, Comi C, Galimberti D, Leone M, Sorosina M, Mescheriakova JY, Hintzen R, Van Duijn C, Bos S, Myhr K-M, Celius EG, Lie B, Spurkland A, Comabella M, Montalban X, Alfredsson L, Stridh P, Hillert J, Jagodic M, Piehl F, Jelcic I, Martin R, Sospedra M, Ban M, Hawkins C, Hysi P, Kalra S, Karpe F, Khadake J, Lachance G, Neville M, Santaniello A, Caillier S, Calabresi P, Cree B, Cross A, Davis M, Haines J, de Bakker P, Delgado S, Dembele M, Edwards K, Hakonarson H, Konidari I, Lathi E, Manrique C, Pericak-Vance M, Piccio L, Schaefer C, McCabe C, Weiner H, Olsson T, Hadjigeorgiou G, Taylor B, Tajoori L, Charlesworth J, Booth D, Harbo HF, Ivinson A, Hauser S, Compston A, Stewart G, Zipp F, Barcellos L, Baranzini S, Martinelli Boneschi F, D’Alfonso S, Ziegler A, Oturai A, McCauley J, Sawcer S, Oksenberg J, De Jager P, Kockum I, Hafler D, Cotsapas C. Low frequency and rare coding variation contributes to multiple sclerosis risk. Cell. 2018;175(6):1679-1687. Scholar
  39. 39.
    Gregory SG, Schmidt S, Seth P, Oksenberg JR, Hart J, Prokop A, Caillier SJ, Ban M, Goris A, Barcellos LF, Lincoln R, McCauley JL, Sawcer SJ, Compston DA, Dubois B, Hauser SL, Garcia-Blanco MA, Pericak-Vance MA, Haines JL, Multiple Sclerosis Genetics Group. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet. 2007;39(9):1083–91. Scholar
  40. 40.
    Gregory AP, Dendrou CA, Attfield KE, Haghikia A, Xifara DK, Butter F, Poschmann G, Kaur G, Lambert L, Leach OA, Promel S, Punwani D, Felce JH, Davis SJ, Gold R, Nielsen FC, Siegel RM, Mann M, Bell JI, McVean G, Fugger L. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature. 2012;488(7412):508–11. Scholar
  41. 41.
    Didonna A, Oksenberg JR. Genetic determinants of risk and progression in multiple sclerosis. Clin Chim Acta. 2015;449:16–22. Scholar
  42. 42.
    Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106–12. Scholar
  43. 43.
    Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6(9):805–15. Scholar
  44. 44.
    Hor JY, Lim TT, Chia YK, Ching YM, Cheah CF, Tan K, Chow HB, Arip M, Eow GB, Easaw PES, Leite MI. Prevalence of neuromyelitis optica spectrum disorder in the multi-ethnic Penang Island, Malaysia, and a review of worldwide prevalence. Mult Scler Relat Disord. 2018;19:20–4. Scholar
  45. 45.
    Matiello M, Kim HJ, Kim W, Brum DG, Barreira AA, Kingsbury DJ, Plant GT, Adoni T, Weinshenker BG. Familial neuromyelitis optica. Neurology. 2010;75(4):310–5. Scholar
  46. 46.
    Matiello M, Schaefer-Klein J, Brum DG, Atkinson EJ, Kantarci OH, Weinshenker BG, NMO Genetics Collaborators. HLA-DRB1∗1501 tagging rs3135388 polymorphism is not associated with neuromyelitis optica. Mult Scler. 2010;16(8):981–4. Scholar
  47. 47.
    Matsushita T, Matsuoka T, Isobe N, Kawano Y, Minohara M, Shi N, Nishimura Y, Ochi H, Kira J. Association of the HLA-DPB1∗0501 allele with anti-aquaporin-4 antibody positivity in Japanese patients with idiopathic central nervous system demyelinating disorders. Tissue Antigens. 2009;73(2):171–6. Scholar
  48. 48.
    Wang H, Dai Y, Qiu W, Zhong X, Wu A, Wang Y, Lu Z, Bao J, Hu X. HLA-DPB1 0501 is associated with susceptibility to anti-aquaporin-4 antibodies positive neuromyelitis optica in southern Han Chinese. J Neuroimmunol. 2011;233(1–2):181–4. Scholar
  49. 49.
    Fukazawa T, Kikuchi S, Miyagishi R, Miyazaki Y, Yabe I, Hamada T, Sasaki H. HLA-dPB1∗0501 is not uniquely associated with opticospinal multiple sclerosis in Japanese patients. Important role of DPB1∗0301. Mult Scler. 2006;12(1):19–23. Scholar
  50. 50.
    Deschamps R, Paturel L, Jeannin S, Chausson N, Olindo S, Bera O, Bellance R, Smadja D, Cesaire D, Cabre P. Different HLA class II (DRB1 and DQB1) alleles determine either susceptibility or resistance to NMO and multiple sclerosis among the French Afro-Caribbean population. Mult Scler. 2011;17(1):24–31. Scholar
  51. 51.
    Estrada K, Whelan CW, Zhao F, Bronson P, Handsaker RE, Sun C, Carulli JP, Harris T, Ransohoff RM, McCarroll SA, Day-Williams AG, Greenberg BM, MacArthur DG. A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica. Nat Commun. 2018;9(1):1929. Scholar
  52. 52.
    Matiello M, Schaefer-Klein JL, Hebrink DD, Kingsbury DJ, Atkinson EJ, Weinshenker BG, NMO Genetics Collaborators. Genetic analysis of aquaporin-4 in neuromyelitis optica. Neurology. 2011;77(12):1149–55. Scholar
  53. 53.
    Crane JM, Rossi A, Gupta T, Bennett JL, Verkman AS. Orthogonal array formation by human aquaporin-4: examination of neuromyelitis optica-associated aquaporin-4 polymorphisms. J Neuroimmunol. 2011;236(1–2):93–8. Scholar
  54. 54.
    Kim JY, Bae JS, Kim HJ, Shin HD. CD58 polymorphisms associated with the risk of neuromyelitis optica in a Korean population. BMC Neurol. 2014;14:57. Scholar
  55. 55.
    Wang X, Yu T, Yan Q, Wang W, Meng N, Li X, Luo Y. Significant association between Fc receptor-like 3 polymorphisms (−1901A>G and -658C>T) and neuromyelitis optica (NMO) susceptibility in the Chinese population. Mol Neurobiol. 2016;53(1):686–94. Scholar
  56. 56.
    Zhuang JC, Wu L, Qian MZ, Cai PP, Liu QB, Zhao GX, Li ZX, Wu ZY. Variants of interleukin-7/interleukin-7 receptor alpha are associated with both neuromyelitis optica and multiple sclerosis among Chinese Han population in southeastern China. Chin Med J. 2015;128(22):3062–8. Scholar
  57. 57.
    Wang H, Zhong X, Wang K, Qiu W, Li J, Dai Y, Hu X. Interleukin 17 gene polymorphism is associated with anti-aquaporin 4 antibody-positive neuromyelitis optica in the southern Han Chinese--a case control study. J Neurol Sci. 2012;314(1–2):26–8. Scholar
  58. 58.
    Al-Araji A, Kidd DP. Neuro-Behcet’s disease: epidemiology, clinical characteristics, and management. Lancet Neurol. 2009;8(2):192–204. Scholar
  59. 59.
    Mendes D, Correia M, Barbedo M, Vaio T, Mota M, Goncalves O, Valente J. Behcet’s disease--a contemporary review. J Autoimmun. 2009;32(3–4):178–88. Scholar
  60. 60.
    Gul A, Inanc M, Ocal L, Aral O, Konice M. Familial aggregation of Behcet’s disease in Turkey. Ann Rheum Dis. 2000;59(8):622–5.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    de Menthon M, Lavalley MP, Maldini C, Guillevin L, Mahr A. HLA-B51/B5 and the risk of Behcet’s disease: a systematic review and meta-analysis of case-control genetic association studies. Arthritis Rheum. 2009;61(10):1287–96. Scholar
  62. 62.
    Mizuki N, Inoko H, Ando H, Nakamura S, Kashiwase K, Akaza T, Fujino Y, Masuda K, Takiguchi M, Ohno S. Behcet’s disease associated with one of the HLA-B51 subantigens, HLA-B∗5101. Am J Ophthalmol. 1993;116(4):406–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Mizuki N, Ohno S, Ando H, Chen L, Palimeris GD, Stavropoulos-Ghiokas E, Ishihara M, Goto K, Nakamura S, Shindo Y, Isobe K, Ito N, Inoko H. A strong association between HLA-B∗5101 and Behcet’s disease in Greek patients. Tissue Antigens. 1997;50(1):57–60.PubMedCrossRefGoogle Scholar
  64. 64.
    Gonzalez-Escribano MF, Rodriguez MR, Walter K, Sanchez-Roman J, Garcia-Lozano JR, Nunez-Roldan A. Association of HLA-B51 subtypes and Behcet’s disease in Spain. Tissue Antigens. 1998;52(1):78–80.PubMedCrossRefGoogle Scholar
  65. 65.
    Kera J, Mizuki N, Ota M, Katsuyama Y, Pivetti-Pezzi P, Ohno S, Inoko H. Significant associations of HLA-B∗5101 and B∗5108, and lack of association of class II alleles with Behcet’s disease in Italian patients. Tissue Antigens. 1999;54(6):565–71.PubMedCrossRefGoogle Scholar
  66. 66.
    Takeno M, Kariyone A, Yamashita N, Takiguchi M, Mizushima Y, Kaneoka H, Sakane T. Excessive function of peripheral blood neutrophils from patients with Behcet’s disease and from HLA-B51 transgenic mice. Arthritis Rheum. 1995;38(3):426–33.PubMedCrossRefGoogle Scholar
  67. 67.
    Ombrello MJ, Kirino Y, de Bakker PI, Gul A, Kastner DL, Remmers EF. Behcet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity. Proc Natl Acad Sci U S A. 2014;111(24):8867–72. Scholar
  68. 68.
    Meguro A, Inoko H, Ota M, Katsuyama Y, Oka A, Okada E, Yamakawa R, Yuasa T, Fujioka T, Ohno S, Bahram S, Mizuki N. Genetics of Behcet disease inside and outside the MHC. Ann Rheum Dis. 2010;69(4):747–54. Scholar
  69. 69.
    Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, Ito N, Kera J, Okada E, Yatsu K, Song YW, Lee EB, Kitaichi N, Namba K, Horie Y, Takeno M, Sugita S, Mochizuki M, Bahram S, Ishigatsubo Y, Inoko H. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behcet’s disease susceptibility loci. Nat Genet. 2010;42(8):703–6. Scholar
  70. 70.
    Remmers EF, Cosan F, Kirino Y, Ombrello MJ, Abaci N, Satorius C, Le JM, Yang B, Korman BD, Cakiris A, Aglar O, Emrence Z, Azakli H, Ustek D, Tugal-Tutkun I, Akman-Demir G, Chen W, Amos CI, Dizon MB, Kose AA, Azizlerli G, Erer B, Brand OJ, Kaklamani VG, Kaklamanis P, Ben-Chetrit E, Stanford M, Fortune F, Ghabra M, Ollier WE, Cho YH, Bang D, O’Shea J, Wallace GR, Gadina M, Kastner DL, Gul A. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet’s disease. Nat Genet. 2010;42(8):698–702. Scholar
  71. 71.
    Iwakura Y, Ishigame H. The IL-23/IL-17 axis in inflammation. J Clin Invest. 2006;116(5):1218–22. Scholar
  72. 72.
    Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O’Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991;146(10):3444–51.PubMedGoogle Scholar
  73. 73.
    Kirino Y, Bertsias G, Ishigatsubo Y, Mizuki N, Tugal-Tutkun I, Seyahi E, Ozyazgan Y, Sacli FS, Erer B, Inoko H, Emrence Z, Cakar A, Abaci N, Ustek D, Satorius C, Ueda A, Takeno M, Kim Y, Wood GM, Ombrello MJ, Meguro A, Gul A, Remmers EF, Kastner DL. Genome-wide association analysis identifies new susceptibility loci for Behcet’s disease and epistasis between HLA-B∗51 and ERAP1. Nat Genet. 2013;45(2):202–7. Scholar
  74. 74.
    Lee YJ, Horie Y, Wallace GR, Choi YS, Park JA, Choi JY, Song R, Kang YM, Kang SW, Baek HJ, Kitaichi N, Meguro A, Mizuki N, Namba K, Ishida S, Kim J, Niemczyk E, Lee EY, Song YW, Ohno S, Lee EB. Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet’s disease. Ann Rheum Dis. 2013;72(9):1510–6. Scholar
  75. 75.
    Li H, Liu Q, Hou S, Du L, Zhou Q, Zhou Y, Kijlstra A, Li Z, Yang P. TNFAIP3 gene polymorphisms confer risk for Behcet’s disease in a Chinese Han population. Hum Genet. 2013;132(3):293–300. Scholar
  76. 76.
    Xavier JM, Shahram F, Sousa I, Davatchi F, Matos M, Abdollahi BS, Sobral J, Nadji A, Oliveira M, Ghaderibarim F, Shafiee NM, Oliveira SA. FUT2: filling the gap between genes and environment in Behcet’s disease? Ann Rheum Dis. 2015;74(3):618–24. Scholar
  77. 77.
    Kappen JH, Medina-Gomez C, van Hagen PM, Stolk L, Estrada K, Rivadeneira F, Uitterlinden AG, Stanford MR, Ben-Chetrit E, Wallace GR, Soylu M, van Laar JA. Genome-wide association study in an admixed case series reveals IL12A as a new candidate in Behcet disease. PLoS One. 2015;10(3):e0119085. Scholar
  78. 78.
    Kirino Y, Zhou Q, Ishigatsubo Y, Mizuki N, Tugal-Tutkun I, Seyahi E, Ozyazgan Y, Ugurlu S, Erer B, Abaci N, Ustek D, Meguro A, Ueda A, Takeno M, Inoko H, Ombrello MJ, Satorius CL, Maskeri B, Mullikin JC, Sun HW, Gutierrez-Cruz G, Kim Y, Wilson AF, Kastner DL, Gul A, Remmers EF. Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behcet disease. Proc Natl Acad Sci U S A. 2013;110(20):8134–9. Scholar
  79. 79.
    Hughes RA, Cornblath DR. Guillain-Barre syndrome. Lancet. 2005;366(9497):1653–66. Scholar
  80. 80.
    Sejvar JJ, Baughman AL, Wise M, Morgan OW. Population incidence of Guillain-Barre syndrome: a systematic review and meta-analysis. Neuroepidemiology. 2011;36(2):123–33. Scholar
  81. 81.
    Geleijns K, Brouwer BA, Jacobs BC, Houwing-Duistermaat JJ, van Duijn CM, van Doorn PA. The occurrence of Guillain-Barre syndrome within families. Neurology. 2004;63(9):1747–50.PubMedCrossRefGoogle Scholar
  82. 82.
    Jin PP, Sun LL, Ding BJ, Qin N, Zhou B, Xia F, Li L, Liu LJ, Liu XD, Zhao G, Wang W, Deng YC, Hou SX. Human leukocyte antigen DQB1 (HLA-DQB1) polymorphisms and the risk for Guillain-Barre syndrome: a systematic review and meta-analysis. PLoS One. 2015;10(7):e0131374. Scholar
  83. 83.
    Schirmer L, Worthington V, Solloch U, Loleit V, Grummel V, Lakdawala N, Grant D, Wassmuth R, Schmidt AH, Gebhardt F, Andlauer TF, Sauter J, Berthele A, Lunn MP, Hemmer B. Higher frequencies of HLA DQB1∗05:01 and anti-glycosphingolipid antibodies in a cluster of severe Guillain-Barre syndrome. J Neurol. 2016;263(10):2105–13. Scholar
  84. 84.
    Blum S, Csurhes P, Reddel S, Spies J, McCombe P. Killer immunoglobulin-like receptor and their HLA ligands in Guillain-Barre Syndrome. J Neuroimmunol. 2014;267(1–2):92–6. Scholar
  85. 85.
    Zhang J, Dong H, Li B, Li CY, Guo L. Association of tumor necrosis factor polymorphisms with Guillain-Barre syndrome. Eur Neurol. 2007;58(1):21–5. Scholar
  86. 86.
    Jahan I, Ahammad RU, Farzana KS, Khalid MM, Islam MB, Rahman MI, Nahar S, Kabir Y, Mohmmad QD, Islam Z. Tumor necrosis factor-alpha -863C/A polymorphism is associated with Guillain-Barre syndrome in Bangladesh. J Neuroimmunol. 2017;310:46–50. Scholar
  87. 87.
    Liu J, Lian Z, Chen H, Shi Z, Feng H, Du Q, Zhang Q, Zhou H. Associations between tumor necrosis factor-alpha gene polymorphisms and the risk of Guillain-Barre syndrome and its subtypes: a systematic review and meta-analysis. J Neuroimmunol. 2017;313:25–33. Scholar
  88. 88.
    Kharwar NK, Prasad KN, Singh K, Paliwal VK, Modi DR. Polymorphisms of IL-17 and ICAM-1 and their expression in Guillain-Barre syndrome. Int J Neurosci. 2017;127(8):680–7. Scholar
  89. 89.
    Van Sorge NM, Van Der Pol W-L, Van De Winkel JGJ. FcγR polymorphisms: implications for function, disease susceptibility and immunotherapy. Tissue Antigens. 2003;61(3):189–202. Scholar
  90. 90.
    van Sorge NM, van der Pol WL, Jansen MD, Geleijns KP, Kalmijn S, Hughes RA, Rees JH, Pritchard J, Vedeler CA, Myhr KM, Shaw C, van Schaik IN, Wokke JH, van Doorn PA, Jacobs BC, van de Winkel JG, van den Berg LH. Severity of Guillain-Barre syndrome is associated with Fc gamma receptor III polymorphisms. J Neuroimmunol. 2005;162(1–2):157–64. Scholar
  91. 91.
    Vedeler CA, Raknes G, Myhr KM, Nyland H. IgG Fc-receptor polymorphisms in Guillain-Barre syndrome. Neurology. 2000;55(5):705–7.PubMedCrossRefGoogle Scholar
  92. 92.
    van der Pol WL, van den Berg LH, Scheepers RH, van der Bom JG, van Doorn PA, van Koningsveld R, van den Broek MC, Wokke JH, van de Winkel JG. IgG receptor IIa alleles determine susceptibility and severity of Guillain-Barre syndrome. Neurology. 2000;54(8):1661–5.PubMedCrossRefGoogle Scholar
  93. 93.
    Dourado MEJ, Ferreira LC, Freire-Neto FP, Jeronimo SM. No association between FCGR2A and FCGR3A polymorphisms in Guillain-Barre Syndrome in a Brazilian population. J Neuroimmunol. 2016;298:160–4. Scholar
  94. 94.
    Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol. 2009;8(5):475–90. Scholar
  95. 95.
    Carr AS, Cardwell CR, McCarron PO, McConville J. A systematic review of population based epidemiological studies in Myasthenia Gravis. BMC Neurol. 2010;10:46. Scholar
  96. 96.
    Lavrnic D, Nikolic A, De Baets M, Verschuuren J, Verduyn W, Losen M, Stojanovic V, Stevic Z, Hajdukovic L, Apostolski S. Familial occurrence of autoimmune myasthenia gravis with different antibody specificity. Neurology. 2008;70(21):2011–3. Scholar
  97. 97.
    Corda D, Deiana GA, Mulargia M, Pirastru MI, Serra M, Piluzza MG, Carcassi C, Sechi G. Familial autoimmune MuSK positive myasthenia gravis. J Neurol. 2011;258(8):1559–60. Scholar
  98. 98.
    Vandiedonck C, Beaurain G, Giraud M, Hue-Beauvais C, Eymard B, Tranchant C, Gajdos P, Dausset J, Garchon HJ. Pleiotropic effects of the 8.1 HLA haplotype in patients with autoimmune myasthenia gravis and thymus hyperplasia. Proc Natl Acad Sci U S A. 2004;101(43):15464–9. Scholar
  99. 99.
    Janer M, Cowland A, Picard J, Campbell D, Pontarotti P, Newsom-Davis J, Bunce M, Welsh K, Demaine A, Wilson AG, Willcox N. A susceptibility region for myasthenia gravis extending into the HLA-class I sector telomeric to HLA-C. Hum Immunol. 1999;60(9):909–17.PubMedCrossRefGoogle Scholar
  100. 100.
    Maniaol AH, Elsais A, Lorentzen AR, Owe JF, Viken MK, Saether H, Flam ST, Brathen G, Kampman MT, Midgard R, Christensen M, Rognerud A, Kerty E, Gilhus NE, Tallaksen CM, Lie BA, Harbo HF. Late onset myasthenia gravis is associated with HLA DRB1∗15:01 in the Norwegian population. PLoS One. 2012;7(5):e36603. Scholar
  101. 101.
    Testi M, Terracciano C, Guagnano A, Testa G, Marfia GA, Pompeo E, Andreani M, Massa R. Association of HLA-DQB1 ∗05:02 and DRB1 ∗16 alleles with late-onset, nonthymomatous, AChR-Ab-positive myasthenia gravis. Autoimmune Dis. 2012;2012:541760. Scholar
  102. 102.
    Giraud M, Beaurain G, Yamamoto AM, Eymard B, Tranchant C, Gajdos P, Garchon HJ. Linkage of HLA to myasthenia gravis and genetic heterogeneity depending on anti-titin antibodies. Neurology. 2001;57(9):1555–60.PubMedCrossRefGoogle Scholar
  103. 103.
    Chen WH, Chiu HC, Hseih RP. Association of HLA-Bw46DR9 combination with juvenile myasthenia gravis in Chinese. J Neurol Neurosurg Psychiatry. 1993;56(4):382–5.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Matsuki K, Juji T, Tokunaga K, Takamizawa M, Maeda H, Soda M, Nomura Y, Segawa M. HLA antigens in Japanese patients with myasthenia gravis. J Clin Invest. 1990;86(2):392–9. Scholar
  105. 105.
    Gregersen PK, Kosoy R, Lee AT, Lamb J, Sussman J, McKee D, Simpfendorfer KR, Pirskanen-Matell R, Piehl F, Pan-Hammarstrom Q, Verschuuren JJ, Titulaer MJ, Niks EH, Marx A, Strobel P, Tackenberg B, Putz M, Maniaol A, Elsais A, Tallaksen C, Harbo HF, Lie BA, Raychaudhuri S, de Bakker PI, Melms A, Garchon HJ, Willcox N, Hammarstrom L, Seldin MF. Risk for myasthenia gravis maps to a (151) Pro-->Ala change in TNIP1 and to human leukocyte antigen-B∗08. Ann Neurol. 2012;72(6):927–35. Scholar
  106. 106.
    Seldin MF, Alkhairy OK, Lee AT, Lamb JA, Sussman J, Pirskanen-Matell R, Piehl F, Verschuuren J, Kostera-Pruszczyk A, Szczudlik P, McKee D, Maniaol AH, Harbo HF, Lie BA, Melms A, Garchon HJ, Willcox N, Gregersen PK, Hammarstrom L. Genome-wide association study of late-onset myasthenia gravis: confirmation of TNFRSF11A and identification of ZBTB10 and three distinct HLA associations. Mol Med. 2016;21(1):769–81. Scholar
  107. 107.
    Renton AE, Pliner HA, Provenzano C, Evoli A, Ricciardi R, Nalls MA, Marangi G, Abramzon Y, Arepalli S, Chong S, Hernandez DG, Johnson JO, Bartoccioni E, Scuderi F, Maestri M, Gibbs JR, Errichiello E, Chio A, Restagno G, Sabatelli M, Macek M, Scholz SW, Corse A, Chaudhry V, Benatar M, Barohn RJ, McVey A, Pasnoor M, Dimachkie MM, Rowin J, Kissel J, Freimer M, Kaminski HJ, Sanders DB, Lipscomb B, Massey JM, Chopra M, Howard JF Jr, Koopman WJ, Nicolle MW, Pascuzzi RM, Pestronk A, Wulf C, Florence J, Blackmore D, Soloway A, Siddiqi Z, Muppidi S, Wolfe G, Richman D, Mezei MM, Jiwa T, Oger J, Drachman DB, Traynor BJ. A genome-wide association study of myasthenia gravis. JAMA Neurol. 2015;72(4):396–404. Scholar
  108. 108.
    Niks EH, Kuks JB, Roep BO, Haasnoot GW, Verduijn W, Ballieux BE, De Baets MH, Vincent A, Verschuuren JJ. Strong association of MuSK antibody-positive myasthenia gravis and HLA-DR14-DQ5. Neurology. 2006;66(11):1772–4. Scholar
  109. 109.
    Bartoccioni E, Scuderi F, Augugliaro A, Chiatamone Ranieri S, Sauchelli D, Alboino P, Marino M, Evoli A. HLA class II allele analysis in MuSK-positive myasthenia gravis suggests a role for DQ5. Neurology. 2009;72(2):195–7. Scholar
  110. 110.
    Alahgholi-Hajibehzad M, Yilmaz V, Gulsen-Parman Y, Aysal F, Oflazer P, Deymeer F, Saruhan-Direskeneli G. Association of HLA-DRB1∗14, -DRB1∗16 and -DQB1∗05 with MuSK-myasthenia gravis in patients from Turkey. Hum Immunol. 2013;74(12):1633–5. Scholar
  111. 111.
    Nikolic AV, Andric ZP, Simonovic RB, Rakocevic Stojanovic VM, Basta IZ, Bojic SD, Lavrnic DV. High frequency of DQB1∗05 and absolute absence of DRB1∗13 in muscle-specific tyrosine kinase positive myasthenia gravis. Eur J Neurol. 2015;22(1):59–63. Scholar
  112. 112.
    Zheng J, Ibrahim S, Petersen F, Yu X. Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue. Genes Immun. 2012;13(8):641–52. Scholar
  113. 113.
    Nanda SK, Venigalla RK, Ordureau A, Patterson-Kane JC, Powell DW, Toth R, Arthur JS, Cohen P. Polyubiquitin binding to ABIN1 is required to prevent autoimmunity. J Exp Med. 2011;208(6):1215–28. Scholar
  114. 114.
    Viken MK, Sollid HD, Joner G, Dahl-Jorgensen K, Ronningen KS, Undlien DE, Flato B, Selvaag AM, Forre O, Kvien TK, Thorsby E, Melms A, Tolosa E, Lie BA. Polymorphisms in the cathepsin L2 (CTSL2) gene show association with type 1 diabetes and early-onset myasthenia gravis. Hum Immunol. 2007;68(9):748–55. Scholar
  115. 115.
    Zhang J, Chen Y, Jia G, Chen X, Lu J, Yang H, Zhou W, Xiao B, Zhang N, Li J. FOXP3-3279 and IVS9+459 polymorphisms are associated with genetic susceptibility to myasthenia gravis. Neurosci Lett. 2013;534:274–8. Scholar
  116. 116.
    Pal Z, Antal P, Millinghoffer A, Hullam G, Paloczi K, Toth S, Gabius HJ, Molnar MJ, Falus A, Buzas EI. A novel galectin-1 and interleukin 2 receptor beta haplotype is associated with autoimmune myasthenia gravis. J Neuroimmunol. 2010;229(1–2):107–11. Scholar
  117. 117.
    Pal Z, Varga Z, Semsei A, Remenyi V, Rozsa C, Falus A, Illes Z, Buzas EI, Molnar MJ. Interleukin-4 receptor alpha polymorphisms in autoimmune myasthenia gravis in a Caucasian population. Hum Immunol. 2012;73(2):193–5. Scholar
  118. 118.
    Alseth EH, Nakkestad HL, Aarseth J, Gilhus NE, Skeie GO. Interleukin-10 promoter polymorphisms in myasthenia gravis. J Neuroimmunol. 2009;210(1–2):63–6. Scholar
  119. 119.
    Huang DR, Pirskanen R, Matell G, Lefvert AK. Tumour necrosis factor-alpha polymorphism and secretion in myasthenia gravis. J Neuroimmunol. 1999;94(1–2):165–71.PubMedCrossRefGoogle Scholar
  120. 120.
    Heckmann JM, Morrison KE, Emeryk-Szajewska B, Strugalska H, Bergoffen J, Willcox N, Newsom-Davis J. Human muscle acetylcholine receptor alpha-subunit gene (CHRNA1) association with autoimmune myasthenia gravis in black, mixed-ancestry and Caucasian subjects. J Autoimmun. 1996;9(2):175–80. Scholar
  121. 121.
    Giraud M, Taubert R, Vandiedonck C, Ke X, Levi-Strauss M, Pagani F, Baralle FE, Eymard B, Tranchant C, Gajdos P, Vincent A, Willcox N, Beeson D, Kyewski B, Garchon HJ. An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus. Nature. 2007;448(7156):934–7. Scholar
  122. 122.
    Dalmau J, Rosenfeld MR. Autoimmune encephalitis update. Neuro-Oncology. 2014;16(6):771–8. Scholar
  123. 123.
    van Sonderen A, Roelen DL, Stoop JA, Verdijk RM, Haasnoot GW, Thijs RD, Wirtz PW, Schreurs MW, Claas FH, Sillevis Smitt PA, Titulaer MJ. Anti-LGI1 encephalitis is strongly associated with HLA-DR7 and HLA-DRB4. Ann Neurol. 2017;81(2):193–8. Scholar
  124. 124.
    Kim TJ, Lee ST, Moon J, Sunwoo JS, Byun JI, Lim JA, Shin YW, Jun JS, Lee HS, Lee WJ, Yang AR, Choi Y, Park KI, Jung KH, Jung KY, Kim M, Lee SK, Chu K. Anti-LGI1 encephalitis is associated with unique HLA subtypes. Ann Neurol. 2017;81(2):183–92. Scholar
  125. 125.
    Mueller SH, Farber A, Pruss H, Melzer N, Golombeck KS, Kumpfel T, Thaler F, Elisak M, Lewerenz J, Kaufmann M, Suhs KW, Ringelstein M, Kellinghaus C, Bien CG, Kraft A, Zettl UK, Ehrlich S, Handreka R, Rostasy K, Then Bergh F, Faiss JH, Lieb W, Franke A, Kuhlenbaumer G, Wandinger KP, Leypoldt F, German Network for Research on Autoimmune Encephalitis (GENERATE). Genetic predisposition in anti-LGI1 and anti-NMDA receptor encephalitis. Ann Neurol. 2018;83(4):863–9. Scholar
  126. 126.
    Koller H, Kieseier BC, Jander S, Hartung HP. Chronic inflammatory demyelinating polyneuropathy. N Engl J Med. 2005;352(13):1343–56. Scholar
  127. 127.
    Stewart GJ, Pollard JD, McLeod JG, Wolnizer CM. HLA antigens in the Landry-Guillain-Barre syndrome and chronic relapsing polyneuritis. Ann Neurol. 1978;4(3):285–9. Scholar
  128. 128.
    Mrad M, Fekih-Mrissa N, Mansour M, Seyah A, Riahi A, Gritli N, Mrissa R. Association of HLA-DR/DQ polymorphism with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in Tunisian patients. Transfus Apher Sci. 2013;49(3):623–6. Scholar
  129. 129.
    Martinez-Martinez L, Lleixa MC, Boera-Carnicero G, Cortese A, Devaux J, Siles A, Rajabally Y, Martinez-Pineiro A, Carvajal A, Pardo J, Delmont E, Attarian S, Diaz-Manera J, Callegari I, Marchioni E, Franciotta D, Benedetti L, Lauria G, de la Calle Martin O, Juarez C, Illa I, Querol L. Anti-NF155 chronic inflammatory demyelinating polyradiculoneuropathy strongly associates to HLA-DRB15. J Neuroinflammation. 2017;14(1):224. Scholar
  130. 130.
    Blum S, Csurhes P, McCombe P. The frequencies of Killer immunoglobulin-like receptors and their HLA ligands in chronic inflammatory demyelinating polyradiculoneuropathy are similar to those in Guillian Barre syndrome but differ from those of controls, suggesting a role for NK cells in pathogenesis. J Neuroimmunol. 2015;285:53–6. Scholar
  131. 131.
    McCombe PA, Clark P, Frith JA, Hammond SR, Stewart GJ, Pollard JD, McLeod JG. Alpha-1 antitrypsin phenotypes in demyelinating disease: an association between demyelinating disease and the allele PiM3. Ann Neurol. 1985;18(4):514–6. Scholar
  132. 132.
    Ali F, Rowley M, Jayakrishnan B, Teuber S, Gershwin ME, Mackay IR. Stiff-person syndrome (SPS) and anti-GAD-related CNS degenerations: protean additions to the autoimmune central neuropathies. J Autoimmun. 2011;37(2):79–87. Scholar
  133. 133.
    Pugliese A, Solimena M, Awdeh ZL, Alper CA, Bugawan T, Erlich HA, De Camilli P, Eisenbarth GS. Association of HLA-DQB1∗0201 with stiff-man syndrome. J Clin Endocrinol Metab. 1993;77(6):1550–3. Scholar
  134. 134.
    Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med. 2004;10. Suppl:S10–7. Scholar
  135. 135.
    Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, DeStafano AL, Bis JC, Beecham GW, Grenier-Boley B, Russo G, Thorton-Wells TA, Jones N, Smith AV, Chouraki V, Thomas C, Ikram MA, Zelenika D, Vardarajan BN, Kamatani Y, Lin CF, Gerrish A, Schmidt H, Kunkle B, Dunstan ML, Ruiz A, Bihoreau MT, Choi SH, Reitz C, Pasquier F, Cruchaga C, Craig D, Amin N, Berr C, Lopez OL, De Jager PL, Deramecourt V, Johnston JA, Evans D, Lovestone S, Letenneur L, Moron FJ, Rubinsztein DC, Eiriksdottir G, Sleegers K, Goate AM, Fievet N, Huentelman MW, Gill M, Brown K, Kamboh MI, Keller L, Barberger-Gateau P, McGuiness B, Larson EB, Green R, Myers AJ, Dufouil C, Todd S, Wallon D, Love S, Rogaeva E, Gallacher J, St George-Hyslop P, Clarimon J, Lleo A, Bayer A, Tsuang DW, Yu L, Tsolaki M, Bossu P, Spalletta G, Proitsi P, Collinge J, Sorbi S, Sanchez-Garcia F, Fox NC, Hardy J, Deniz Naranjo MC, Bosco P, Clarke R, Brayne C, Galimberti D, Mancuso M, Matthews F, European Alzheimer’s Disease Initiative (EADI), Genetic and Environmental Risk in Alzheimer’s Disease (GERAD), Alzheimer’s Disease Genetic Consortium (ADGC), Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), Moebus S, Mecocci P, Del Zompo M, Maier W, Hampel H, Pilotto A, Bullido M, Panza F, Caffarra P, Nacmias B, Gilbert JR, Mayhaus M, Lannefelt L, Hakonarson H, Pichler S, Carrasquillo MM, Ingelsson M, Beekly D, Alvarez V, Zou F, Valladares O, Younkin SG, Coto E, Hamilton-Nelson KL, Gu W, Razquin C, Pastor P, Mateo I, Owen MJ, Faber KM, Jonsson PV, Combarros O, O’Donovan MC, Cantwell LB, Soininen H, Blacker D, Mead S, Mosley TH Jr, Bennett DA, Harris TB, Fratiglioni L, Holmes C, de Bruijn RF, Passmore P, Montine TJ, Bettens K, Rotter JI, Brice A, Morgan K, Foroud TM, Kukull WA, Hannequin D, Powell JF, Nalls MA, Ritchie K, Lunetta KL, Kauwe JS, Boerwinkle E, Riemenschneider M, Boada M, Hiltuenen M, Martin ER, Schmidt R, Rujescu D, Wang LS, Dartigues JF, Mayeux R, Tzourio C, Hofman A, Nothen MM, Graff C, Psaty BM, Jones L, Haines JL, Holmans PA, Lathrop M, Pericak-Vance MA, Launer LJ, Farrer LA, van Duijn CM, Van Broeckhoven C, Moskvina V, Seshadri S, Williams J, Schellenberg GD, Amouyel P. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet. 2013;45(12):1452–8. Scholar
  136. 136.
    Jiao B, Liu X, Zhou L, Wang MH, Zhou Y, Xiao T, Zhang W, Sun R, Waye MM, Tang B, Shen L. Polygenic analysis of late-onset Alzheimer’s disease from Mainland China. PLoS One. 2015;10(12):e0144898. Scholar
  137. 137.
    Allen M, Kachadoorian M, Carrasquillo MM, Karhade A, Manly L, Burgess JD, Wang C, Serie D, Wang X, Siuda J, Zou F, Chai HS, Younkin C, Crook J, Medway C, Nguyen T, Ma L, Malphrus K, Lincoln S, Petersen RC, Graff-Radford NR, Asmann YW, Dickson DW, Younkin SG, Ertekin-Taner N. Late-onset Alzheimer disease risk variants mark brain regulatory loci. Neurol Genet. 2015;1(2):e15. Scholar
  138. 138.
    Steele NZ, Carr JS, Bonham LW, Geier EG, Damotte V, Miller ZA, Desikan RS, Boehme KL, Mukherjee S, Crane PK, Kauwe JS, Kramer JH, Miller BL, Coppola G, Hollenbach JA, Huang Y, Yokoyama JS. Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: a case-control study. PLoS Med. 2017;14(3):e1002272. Scholar
  139. 139.
    Hamza TH, Zabetian CP, Tenesa A, Laederach A, Montimurro J, Yearout D, Kay DM, Doheny KF, Paschall J, Pugh E, Kusel VI, Collura R, Roberts J, Griffith A, Samii A, Scott WK, Nutt J, Factor SA, Payami H. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease. Nat Genet. 2010;42(9):781–5. Scholar
  140. 140.
    International Parkinson Disease Genomics Consortium (IPDGC). Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet. 2011;377(9766):641–9. Scholar
  141. 141.
    Ahmed I, Tamouza R, Delord M, Krishnamoorthy R, Tzourio C, Mulot C, Nacfer M, Lambert JC, Beaune P, Laurent-Puig P, Loriot MA, Charron D, Elbaz A. Association between Parkinson’s disease and the HLA-DRB1 locus. Mov Disord. 2012;27(9):1104–10. Scholar
  142. 142.
    Wissemann WT, Hill-Burns EM, Zabetian CP, Factor SA, Patsopoulos N, Hoglund B, Holcomb C, Donahue RJ, Thomson G, Erlich H, Payami H. Association of Parkinson disease with structural and regulatory variants in the HLA region. Am J Hum Genet. 2013;93(5):984–93. Scholar
  143. 143.
    International Multiple Sclerosis Genetics Consortium (IMSGC). Network-based multiple sclerosis pathway analysis with GWAS data from 15,000 cases and 30,000 controls. Am J Hum Genet. 2013;92(6):854–65. Scholar
  144. 144.
    Birling MC, Herault Y, Pavlovic G. Modeling human disease in rodents by CRISPR/Cas9 genome editing. Mamm Genome. 2017;28(7–8):291–301. Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Neurology and Weill Institute for NeurosciencesUniversity of California at San FranciscoSan FranciscoUSA

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