Genetic basis of myasthenia gravis - A comprehensive review

Journal of Autoimmunity

Volumn 52, Issue , 2014, Pages 146-153

  Avidan, Nili ^a   Le Panse, Rozen ^b   Berrih Aknin, Sonia ^b   Miller, Ariel ^a,c  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^b Sorbonne Université   (France)

^c CARMEL MEDICAL CENTER   (Israel)

Author keywords

Epigenetic; Gender; Genetics; Myasthenia gravis; NF B signaling pathway; TNIP1

Indexed keywords

CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; HLA ANTIGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE 22; SEX HORMONE; TRANSCRIPTION FACTOR FOXP3; TUMOR NECROSIS FACTOR ALPHA; BIOLOGICAL MARKER; MICRORNA; PROTEIN TYROSINE PHOSPHATASE; TNFAIP3 INTERACTING PROTEIN 1; TYROSINE PHOSPHATASE NON RECEPTOR 22; UNCLASSIFIED DRUG; DNA BINDING PROTEIN; PTPN22 PROTEIN, HUMAN; TNIP1 PROTEIN, HUMAN;

ALLELE; AUTOIMMUNE DISEASE; ENVIRONMENTAL FACTOR; EPIGENETICS; FAMILIAL DISEASE; GENDER BIAS; GENE FREQUENCY; GENE MUTATION; GENE STRUCTURE; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC RISK; GENETIC SUSCEPTIBILITY; HUMAN; LYMPHOCYTE DIFFERENTIATION; MYASTHENIA GRAVIS; PREVALENCE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; RISK FACTOR; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; TWINS; AUTOIMMUNITY; DISEASE COURSE; DISEASE MARKER; EARLY ONSTE MYASTHENIA GRAVIS; HLA SYSTEM; NEUROMUSCULAR SYNAPSE; ONSET AGE; PATHOPHYSIOLOGY; POSTSYNAPTIC MEMBRANE; RARE DISEASE; SEX DIFFERENCE; T LYMPHOCYTE ACTIVATION; TWIN CONCORDANCE; CELL DIFFERENTIATION; GENETIC EPIGENESIS; GENETIC POLYMORPHISM; GENETIC PREDISPOSITION; GENETICS; GENOTYPE ENVIRONMENT INTERACTION; IMMUNOLOGY; METABOLISM;

CELL DIFFERENTIATION; DNA-BINDING PROTEINS; EPIGENESIS, GENETIC; GENE-ENVIRONMENT INTERACTION; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HLA ANTIGENS; HUMANS; MYASTHENIA GRAVIS; NF-KAPPA B; POLYMORPHISM, GENETIC; PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 22; SEX FACTORS; SIGNAL TRANSDUCTION; T-LYMPHOCYTES, REGULATORY;

EID: 84904365931     PISSN: 08968411     EISSN: 10959157     Source Type: Journal    
DOI: 10.1016/j.jaut.2013.12.001     Document Type: Review

References (125)

1. Meriggioli M.N., Sanders D.B. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol 2009, 8:475-490.
2. Lindstrom J.M., Seybold M.E., Lennon V.A., Whittingham S., Duane D.D. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology 1976, 26:1054-1059.
3. Shigemoto K., Kubo S., Maruyama N., Hato N., Yamada H., Jie C., et al. Induction of myasthenia by immunization against muscle-specific kinase. JClin Invest 2006, 116:1016-1024.
4. Cavalcante P., le Panse R., Berrih-Aknin S., Maggi L., Antozzi C., Baggi F., et al. The thymus in myasthenia gravis: site of "innate autoimmunity"?. Muscle Nerve 2011, 44:467-484.
5. Engel A.G., Fumagalli G. Mechanisms of acetylcholine receptor loss from the neuromuscular junction. Ciba Found Symp 1982, 197-224.
6. Poea-Guyon S., Christadoss P., Le Panse R., Guyon T., De Baets M., Wakkach A., et al. Effects of cytokines on acetylcholine receptor expression: implications for myasthenia gravis. JImmunol 2005, 174:5941-5949.
7. Cufi P., Dragin N., Weiss J.M., Martinez-Martinez P., De Baets M.H., Roussin R., et al. Implication of double-stranded RNA signaling in the etiology of autoimmune myasthenia gravis. Ann Neurol 2013, 73:281-293.
8. Le Panse R., Cizeron-Clairac G., Cuvelier M., Truffault F., Bismuth J., Nancy P., et al. Regulatory and pathogenic mechanisms in human autoimmune myasthenia gravis. Ann N Y Acad Sci 2008, 1132:135-142.
9. Masuda M., Matsumoto M., Tanaka S., Nakajima K., Yamada N., Ido N., et al. Clinical implication of peripheral CD4+CD25+ regulatory T cells and Th17 cells in myasthenia gravis patients. JNeuroimmunol 2010, 225:123-131.
10. Querol L., Illa I. Myasthenia gravis and the neuromuscular junction. Curr Opin Neurol 2013, 26:459-465.
11. Carr A.S., Cardwell C.R., McCarron P.O., McConville J. Asystematic review of population based epidemiological studies in Myasthenia Gravis. BMC Neurol 2010, 10:46.
12. Montomoli C., Citterio A., Piccolo G., Cioccale R., Ferretti V.V., Fratti C., et al. Epidemiology and geographical variation of myasthenia gravis in the province of Pavia, Italy. Neuroepidemiology 2012, 38:100-105.
13. Casetta I., Groppo E., De Gennaro R., Cesnik E., Piccolo L., Volpato S., et al. Myasthenia gravis: a changing pattern of incidence. JNeurol 2010, 257:2015-2019.
14. Gattellari M., Goumas C., Worthington J.M. Anational epidemiological study of myasthenia gravis in Australia. Eur J Neurol 2012, 19:1413-1420.
15. Murai H., Yamashita N., Watanabe M., Nomura Y., Motomura M., Yoshikawa H., et al. Characteristics of myasthenia gravis according to onset-age: Japanese nationwide survey. JNeurol Sci 2011, 305:97-102.
16. Lai C.H., Tseng H.F. Nationwide population-based epidemiological study of myasthenia gravis in Taiwan. Neuroepidemiology 2010, 35:66-71.
17. Pallaver F., Riviera A.P., Piffer S., Ricciardi R., Roni R., Orrico D., et al. Change in myasthenia gravis epidemiology in Trento, Italy, after twenty years. Neuroepidemiology 2011, 36:282-287.
18. Kalb B., Matell G., Pirskanen R., Lambe M. Epidemiology of myasthenia gravis: a population-based study in Stockholm, Sweden. Neuroepidemiology 2002, 21:221-225.
19. Wang W., Chen Y.P., Wang Z.K., Wei D.N., Yin L. Acohort study on myasthenia gravis patients in China. Neurol Sci 2013, 34:1759-1764.
20. Lavrnic D., Nikolic A., De Baets M., Verschuuren J., Verduyn W., Losen M., et al. Familial occurrence of autoimmune myasthenia gravis with different antibody specificity. Neurology 2008, 70:2011-2013.
21. Corda D., Deiana G.A., Mulargia M., Pirastru M.I., Serra M., Piluzza M.G., et al. Familial autoimmune MuSK positive myasthenia gravis. JNeurol 2011, 258:1559-1560.
22. Feng H.Y., Liu W.B., Luo C.M., Yang L.X., Fang W., Qiu L., et al. Aretrospective review of 15 patients with familial myasthenia gravis over a period of 25 years. Neurol Sci 2011, 33(4):771-777.
23. Li F., Szobor A., Croxen R., Anselmo V., Yuan Q.P., Lindblad K., et al. Dominantly inherited familial myasthenia gravis as a separate genetic entity without involvement of defined candidate gene loci. Int J Mol Med 2001, 7:289-294.
24. Szobor A. Familial myasthenia gravis: nine patients in two generations. Acta Med Hung 1991, 48:145-149.
25. Landoure G., Knight M.A., Stanescu H., Taye A.A., Shi Y., Diallo O., et al. Acandidate gene for autoimmune myasthenia gravis. Neurology 2012, 79:342-347.
26. Mao Z.F., Yang L.X., Mo X.A., Qin C., Lai Y.R., He N.Y., et al. Frequency of autoimmune diseases in myasthenia gravis: a systematic review. Int J Neurosci 2011, 121:121-129.
27. Nakata R., Motomura M., Masuda T., Shiraishi H., Tokuda M., Fukuda T., et al. Thymus histology and concomitant autoimmune diseases in Japanese patients with muscle-specific receptor tyrosine kinase-antibody-positive myasthenia gravis. Eur J Neurol 2013, 20:1272-1276.
28. Ramanujam R., Piehl F., Pirskanen R., Gregersen P.K., Hammarstrom L. Concomitant autoimmunity in myasthenia gravis-lack of association with IgA deficiency. JNeuroimmunol 2011, 236:118-122.
29. Horton R., Gibson R., Coggill P., Miretti M., Allcock R.J., Almeida J., et al. Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project. Immunogenetics 2008, 60:1-18.
30. Vandiedonck C., Beaurain G., Giraud M., Hue-Beauvais C., Eymard B., Tranchant C., et al. 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, 101:15464-15469.
31. Giraud M., Beaurain G., Eymard B., Tranchant C., Gajdos P., Garchon H.J. Genetic control of autoantibody expression in autoimmune myasthenia gravis: role of the self-antigen and of HLA-linked loci. Genes Immun 2004, 5:398-404.
32. Janer M., Cowland A., Picard J., Campbell D., Pontarotti P., Newsom-Davis J., et al. Asusceptibility region for myasthenia gravis extending into the HLA-class I sector telomeric to HLA-C. Hum Immunol 1999, 60:909-917.
33. Suzuki S., Utsugisawa K., Nagane Y., Satoh T., Kuwana M., Suzuki N. Clinical and immunological differences between early and late-onset myasthenia gravis in Japan. JNeuroimmunol 2011, 230:148-152.
34. Candore G., Modica M.A., Lio D., Colonna-Romano G., Listi F., Grimaldi M.P., et al. Pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype: a genetically determined defect of C4 influences immunological parameters of healthy carriers of the haplotype. Biomed Pharmacother 2003, 57:274-277.
35. Candore G., Lio D., Colonna Romano G., Caruso C. Pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype: effect of multiple gene interactions. Autoimmun Rev 2002, 1:29-35.
36. Zhu W.H., Lu J.H., Lin J., Xi J.Y., Lu J., Luo S.S., et al. HLA-DQA1*03:02/DQB1*03:03:02 is strongly associated with susceptibility to childhood-onset ocular myasthenia gravis in Southern Han Chinese. JNeuroimmunol 2012, 247:81-85.
37. Maniaol A.H., Elsais A., Lorentzen A.R., Owe J.F., Viken M.K., Saether H., et al. Late onset myasthenia gravis is associated with HLA DRB1*15:01 in the Norwegian population. PLoS One 2012, 7:e36603.
38. Bartoccioni E., Scuderi F., Augugliaro A., Chiatamone Ranieri S., Sauchelli D., Alboino P., et al. HLA class II allele analysis in MuSK-positive myasthenia gravis suggests a role for DQ5. Neurology 2009, 72:195-197.
39. Xie Y.C., Qu Y., Sun L., Li H.F., Zhang H., Shi H.J., et al. Association between HLA-DRB1 and myasthenia gravis in a northern Han Chinese population. JClin Neurosci 2011, 18:1524-1527.
40. Testi M., Terracciano C., Guagnano A., Testa G., Marfia G.A., Pompeo E., et al. Association of HLA-DQB1 *05:02 and DRB1 *16 alleles with late-onset, nonthymomatous, AChR-Ab-positive myasthenia gravis. Autoimmune Dis 2012, 2012:541760.
41. Niks E.H., Kuks J.B., Roep B.O., Haasnoot G.W., Verduijn W., Ballieux B.E., et al. Strong association of MuSK antibody-positive myasthenia gravis and HLA-DR14-DQ5. Neurology 2006, 66:1772-1774.
42. Kroeger K.M., Carville K.S., Abraham L.J. The -308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol 1997, 34:391-399.
43. Rodriguez-Carreon A.A., Zuniga J., Hernandez-Pacheco G., Rodriguez-Perez J.M., Perez-Hernandez N., Montes de Oca J.V., et al. Tumor necrosis factor-alpha-308 promoter polymorphism contributes independently to HLA alleles in the severity of rheumatoid arthritis in Mexicans. JAutoimmun 2005, 24:63-68.
44. O'Keefe G.E., Hybki D.L., Munford R.S. The G→A single nucleotide polymorphism at the -308 position in the tumor necrosis factor-alpha promoter increases the risk for severe sepsis after trauma. JTrauma 2002, 52:817-825. discussion 25-6.
45. Elahi M.M., Asotra K., Matata B.M., Mastana S.S. Tumor necrosis factor alpha -308 gene locus promoter polymorphism: an analysis of association with health and disease. Biochim Biophys Acta 2009, 1792:163-172.
46. Hong Y., Ge Z., Jing C., Shi J., Dong X., Zhou F., et al. Functional promoter-308G>A variant in tumor necrosis factor alpha gene is associated with risk and progression of gastric cancer in a Chinese population. PLoS One 2013, 8:e50856.
47. Huang D.R., Pirskanen R., Matell G., Lefvert A.K. Tumour necrosis factor-alpha polymorphism and secretion in myasthenia gravis. JNeuroimmunol 1999, 94:165-171.
48. Skeie G.O., Pandey J.P., Aarli J.A., Gilhus N.E. TNFA and TNFB polymorphisms in myasthenia gravis. Arch Neurol 1999, 56:457-461.
49. Zelano G., Lino M.M., Evoli A., Settesoldi D., Batocchi A.P., Torrente I., et al. Tumour necrosis factor beta gene polymorphisms in myasthenia gravis. Eur J Immunogenet 1998, 25:403-408.
50. Raychaudhuri S., Sandor C., Stahl E.A., Freudenberg J., Lee H.S., Jia X., et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet 2012, 44:291-296.
51. Barrett J.C. From HLA association to function. Nat Genet 2012, 44:235-236.
52. Hu X., Daly M. What have we learned from six years of GWAS in autoimmune diseases, and what is next?. Curr Opin Immunol 2012, 24:571-575.
53. Visscher P.M., Brown M.A., McCarthy M.I., Yang J. Five years of GWAS discovery. Am J Hum Genet 2012, 90:7-24.
54. Gregersen P.K., Kosoy R., Lee A.T., Lamb J., Sussman J., McKee D., et al. Risk for myasthenia gravis maps to a (151) Pro→Ala change in TNIP1 and to human leukocyte antigen-B*08. Ann Neurol 2012, 72:927-935.
55. Adrianto I., Wang S., Wiley G.B., Lessard C.J., Kelly J.A., Adler A.J., et al. Association of two independent functional risk haplotypes in TNIP1 with systemic lupus erythematosus. Arthritis Rheum 2012, 64:3695-3705.
56. Lessard C.J., Li H., Adrianto I., Ice J.A., Rasmussen A., Grundahl K.M., et al. Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome. Nat Genet 2013, 45:1284-1292.
57. Ramirez V.P., Gurevich I., Aneskievich B.J. Emerging roles for TNIP1 in regulating post-receptor signaling. Cytokine Growth Factor Rev 2012, 23:109-118.
58. Oshima S., Turer E.E., Callahan J.A., Chai S., Advincula R., Barrera J., et al. ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development. Nature 2009, 457:906-909.
59. Wagner S., Carpentier I., Rogov V., Kreike M., Ikeda F., Lohr F., et al. Ubiquitin binding mediates the NF-kappaB inhibitory potential of ABIN proteins. Oncogene 2008, 27:3739-3745.
60. Lefvert A.K., Zhao Y., Ramanujam R., Yu S., Pirskanen R., Hammarstrom L. PTPN22 R620W promotes production of anti-AChR autoantibodies and IL-2 in myasthenia gravis. JNeuroimmunol 2008, 197:110-113.
61. Vandiedonck C., Capdevielle C., Giraud M., Krumeich S., Jais J.P., Eymard B., et al. Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis. Ann Neurol 2006, 59:404-407.
62. Lee Y.H., Rho Y.H., Choi S.J., Ji J.D., Song G.G., Nath S.K., et al. The PTPN22 C1858T functional polymorphism and autoimmune diseases-a meta-analysis. Rheumatology (Oxford) 2007, 46:49-56.
63. Bottini N., Musumeci L., Alonso A., Rahmouni S., Nika K., Rostamkhani M., et al. Afunctional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 2004, 36:337-338.
64. Begovich A.B., Carlton V.E., Honigberg L.A., Schrodi S.J., Chokkalingam A.P., Alexander H.C., et al. Amissense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 2004, 75:330-337.
65. Greve B., Hoffmann P., Illes Z., Rozsa C., Berger K., Weissert R., et al. The autoimmunity-related polymorphism PTPN22 1858C/T is associated with anti-titin antibody-positive myasthenia gravis. Hum Immunol 2009, 70:540-542.
66. Smyth D.J., Plagnol V., Walker N.M., Cooper J.D., Downes K., Yang J.H., et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. NEngl J Med 2008, 359:2767-2777.
67. Kurko J., Besenyei T., Laki J., Glant T.T., Mikecz K., Szekanecz Z. Genetics of rheumatoid arthritis - a comprehensive review. Clin Rev Allergy Immunol 2013, 45(2):170-179.
68. Ploski R., Szymanski K., Bednarczuk T. The genetic basis of graves' disease. Curr Genomics 2011, 12:542-563.
69. Strobel P., Chuang W.Y., Chuvpilo S., Zettl A., Katzenberger T., Kalbacher H., et al. Common cellular and diverse genetic basis of thymoma-associated myasthenia gravis: role of MHC class II and AIRE genes and genetic polymorphisms. Ann N Y Acad Sci 2008, 1132:143-156.
70. Wang X.B., Pirskanen R., Giscombe R., Lefvert A.K. Two SNPs in the promoter region of the CTLA-4 gene affect binding of transcription factors and are associated with human myasthenia gravis. JIntern Med 2008, 263:61-69.
71. Gu M., Kakoulidou M., Giscombe R., Pirskanen R., Lefvert A.K., Klareskog L., et al. Identification of CTLA-4 isoforms produced by alternative splicing and their association with myasthenia gravis. Clin Immunol 2008, 128:374-381.
72. Josefowicz S.Z., Lu L.F., Rudensky A.Y. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 2012, 30:531-564.
73. Zhang J., Chen Y., Jia G., Chen X., Lu J., Yang H., et al. FOXP3-3279 and IVS9+459 polymorphisms are associated with genetic susceptibility to myasthenia gravis. Neurosci Lett 2013, 534:274-278.
74. Balandina A., Lecart S., Dartevelle P., Saoudi A., Berrih-Aknin S. Functional defect of regulatory CD4(+)CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis. Blood 2005, 105:735-741.
75. Itier V., Bertrand D. Neuronal nicotinic receptors: from protein structure to function. FEBS Lett 2001, 504:118-125.
76. Bonifati D.M., Willcox N., Vincent A., Beeson D. Lack of association between acetylcholine receptor epsilon polymorphisms and early-onset myasthenia gravis. Muscle Nerve 2004, 29:436-439.
77. Djabiri F., Gajdos P., Eymard B., Gomez L., Bach J.F., Garchon H.J. No evidence for an association of AChR beta-subunit gene (CHRNB1) with myasthenia gravis. JNeuroimmunol 1997, 78:86-89.
78. Giraud M., Eymard B., Tranchant C., Gajdos P., Garchon H.J. Association of the gene encoding the delta-subunit of the muscle acetylcholine receptor (CHRND) with acquired autoimmune myasthenia gravis. Genes Immun 2004, 5:80-83.
79. Heckmann J.M., Morrison K.E., Emeryk-Szajewska B., Strugalska H., Bergoffen J., Willcox N., et al. Human muscle acetylcholine receptor alpha-subunit gene (CHRNA1) association with autoimmune myasthenia gravis in black, mixed-ancestry and Caucasian subjects. JAutoimmun 1996, 9:175-180.
80. Wilisch A., Gutsche S., Hoffacker V., Schultz A., Tzartos S., Nix W., et al. Association of acetylcholine receptor alpha-subunit gene expression in mixed thymoma with myasthenia gravis. Neurology 1999, 52:1460-1466.
81. Giraud M., Taubert R., Vandiedonck C., Ke X., Levi-Strauss M., Pagani F., et al. An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus. Nature 2007, 448:934-937.
82. Bogdanos D.P., Smyk D.S., Rigopoulou E.I., Mytilinaiou M.G., Heneghan M.A., Selmi C., et al. Twin studies in autoimmune disease: genetics, gender and environment. JAutoimmun 2012, 38:J156-J169.
83. Ramanujam R., Pirskanen R., Ramanujam S., Hammarstrom L. Utilizing twins concordance rates to infer the predisposition to myasthenia gravis. Twin Res Hum Genet 2011, 14:129-136.
84. Namba T., Shapiro M.S., Brunner N.G., Grob D. Myasthenia gravis occurring in twins. JNeurol Neurosurg Psychiatr 1971, 34:531-534.
85. Agafonov B.V., Tsuman V.G., Shagal D.I., Sidorova O.P., Sibiriakova L.G., Lebedeva L.L., et al. Twin studies of myasthenia. Zh Nevrol Psikhiatr Im S S Korsakova 1997, 97:18-21.
86. Singh R.P., Massachi I., Manickavel S., Singh S., Rao N.P., Hasan S., et al. The role of miRNA in inflammation and autoimmunity. Autoimmun Rev 2013, 12:1160-1165.
87. Le Panse R., Berrih-Aknin S. Autoimmune myasthenia gravis: autoantibody mechanisms and new developments on immune regulation. Curr Opin Neurol 2013, 26:569-576.
88. De Santis M., Selmi C. The therapeutic potential of epigenetics in autoimmune diseases. Clin Rev Allergy Immunol 2012, 42:92-101.
89. Hedrich C.M., Tsokos G.C. Epigenetic mechanisms in systemic lupus erythematosus and other autoimmune diseases. Trends Mol Med 2011, 17:714-724.
90. Cheng Z., Qiu S., Jiang L., Zhang A., Bao W., Liu P., et al. MiR-320a is downregulated in patients with myasthenia gravis and modulates inflammatory cytokines production by targeting mitogen-activated protein kinase 1. JClin Immunol 2013, 33:567-576.
91. Jiang L., Cheng Z., Qiu S., Que Z., Bao W., Jiang C., et al. Altered let-7 expression in myasthenia gravis and let-7c mediated regulation of IL-10 by directly targeting IL-10 in Jurkat cells. Int Immunopharmacol 2012, 14:217-223.
92. Wang J., Zheng S., Xin N., Dou C., Fu L., Zhang X., et al. Identification of novel microRNA signatures linked to experimental autoimmune myasthenia gravis pathogenesis: down-regulated miR-145 promotes pathogenetic Th17 cell response. JNeuroimmune Pharmacol 2013, 8(5):1287-1302.
93. Mays J., Butts C.L. Intercommunication between the neuroendocrine and immune systems: focus on myasthenia gravis. Neuroimmunomodulation 2011, 18:320-327.
94. Nancy P., Berrih-Aknin S. Differential estrogen receptor expression in autoimmune myasthenia gravis. Endocrinology 2005, 146:2345-2353.
95. Delpy L., Douin-Echinard V., Garidou L., Bruand C., Saoudi A., Guery J.C. Estrogen enhances susceptibility to experimental autoimmune myasthenia gravis by promoting type 1-polarized immune responses. JImmunol 2005, 175:5050-5057.
96. Kaur M., Schmeier S., MacPherson C.R., Hofmann O., Hide W.A., Taylor S., et al. Prioritizing genes of potential relevance to diseases affected by sex hormones: an example of myasthenia gravis. BMC Genomics 2008, 9:481.
97. Sathyabama S., Khan N., Agrewala J.N. Friendly pathogens: prevent or provoke autoimmunity. Crit Rev Microbiol 2013, Ahead of Print: Pages 1-8.
98. Yurkovetskiy L., Burrows M., Khan A.A., Graham L., Volchkov P., Becker L., et al. Gender bias in autoimmunity is influenced by microbiota. Immunity 2013, 39:400-412.
99. Liu L.Y., Schaub M.A., Sirota M., Butte A.J. Sex differences in disease risk from reported genome-wide association study findings. Hum Genet 2012, 131:353-364.
100. Porcu E., Medici M., Pistis G., Volpato C.B., Wilson S.G., Cappola A.R., et al. Ameta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function. PLoS Genet 2013, 9:e1003266.
101. Rossin E.J., Lage K., Raychaudhuri S., Xavier R.J., Tatar D., Benita Y., et al. Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology. PLoS Genet 2011, 7:e1001273.
102. Consortium IMSG Network-based multiple sclerosis pathway analysis with GWAS data from 15,000 cases and 30,000 controls. Am J Hum Genet 2013, 92(6):854-865.
103. Jostins L., Ripke S., Weersma R.K., Duerr R.H., McGovern D.P., Hui K.Y., et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012, 491:119-124.
104. Viken M.K., Sollid H.D., Joner G., Dahl-Jorgensen K., Ronningen K.S., Undlien D.E., et al. Polymorphisms in the cathepsin L2 (CTSL2) gene show association with type 1 diabetes and early-onset myasthenia gravis. Hum Immunol 2007, 68:748-755.
105. Provenzano C., Ricciardi R., Scuderi F., Maiuri M.T., Maestri M., La Carpia F., et al. PTPN22 and myasthenia gravis: replication in an Italian population and meta-analysis of literature data. Neuromuscul Disord 2012, 22:131-138.
106. Pal Z., Antal P., Millinghoffer A., Hullam G., Paloczi K., Toth S., et al. Anovel galectin-1 and interleukin 2 receptor beta haplotype is associated with autoimmune myasthenia gravis. JNeuroimmunol 2010, 229:107-111.
107. Yilmaz V., Tutuncu Y., Baris Hasbal N., Parman Y., Serdaroglu P., Deymeer F., et al. Polymorphisms of interferon-gamma, interleukin-10, and interleukin-12 genes in myasthenia gravis. Hum Immunol 2007, 68:544-549.
108. Pal Z., Varga Z., Semsei A., Remenyi V., Rozsa C., Falus A., et al. Interleukin-4 receptor alpha polymorphisms in autoimmune myasthenia gravis in a Caucasian population. Hum Immunol 2012, 73:193-195.
109. Alseth E.H., Nakkestad H.L., Aarseth J., Gilhus N.E., Skeie G.O. Interleukin-10 promoter polymorphisms in myasthenia gravis. JNeuroimmunol 2009, 210:63-66.
110. Zagoriti Z., Georgitsi M., Giannakopoulou O., Ntellos F., Tzartos S.J., Patrinos G.P., et al. Genetics of myasthenia gravis: a case-control association study in the Hellenic population. Clin Dev Immunol 2012, 2012:484919.
111. Alter M., Talbert O.R. Myasthenia gravis in one monozygotic twin. Neurology 1960, 10:793-798.
112. Osborne D., Simcock J. Myasthenia gravis in identical twins. Br Med J 1966, 1:1025-1026.
113. Motoki R., Harada M., Chiba A., Honda K. Acase of myasthenia gravis of identical twin brothers. Int Surg 1966, 45:674-677.
114. Herrmann C. The familial occurrence of myasthenia gravis. Ann N Y Acad Sci 1971, 183:334-350.
115. Michalski J.P., Snyder S.M., McLeod R.L., Talal N. Monozygotic twins with Klinefelter's syndrome discordant for systemic lupus erythematosus and symptomatic myasthenia gravis. Arthritis Rheum 1978, 21:306-309.
116. Allen N., Kissel P., Pietrasiuk D., Perlow M.J. Myasthenia gravis in monozygotic twins. Clinical follow-up nine years after thymectomy. Arch Neurol 1984, 41:994-996.
117. Vasil'ev V.N., Sirotina V.V., Shabanova L.F., Egorova I.E. Thymectomy for myasthenia in twin sisters. Vestn Khir Im I I Grek 1984, 133:75-76.
118. Murphy J., Murphy S.F. Myasthenia gravis in identical twins. Neurology 1986, 36:78-80.
119. Lefvert A.K., Pirskanen R., Eng H., Sundewall A.C., Svanborg E. Bcell and autoantibody repertoire in a pair of monozygotic twins discordant for myasthenia gravis. Clin Immunol Immunopathol 1989, 53:161-170.
120. Dias-Tosta E., Aguiar M.F., Barbosa H., Vilela S.S. Familial myasthenia gravis: a case report in identical twins. Arq Neuropsiquiatr 1989, 47:248-253.
121. Grinlinton F.M., Lynch N.M., Hart H.H. Apair of monozygotic twins who are concordant for myasthenia gravis but became discordant for systemic lupus erythematosus post-thymectomy. Arthritis Rheum 1991, 34:916-919.
122. Theile U., Kessler S. Effect of heredity and environment in immune diseases. Presentation of twin data. Med Klin (Munich) 1994, 89:312-318.
123. Kakoulidou M., Ahlberg R., Yi Q., Giscombe R., Pirskanen R., Lefvert A.K. The autoimmune T and B cell repertoires in monozygotic twins discordant for myasthenia gravis. JNeuroimmunol 2004, 148:183-191.
124. Punga A.R., Nygren I., Askmark H., Stalberg E.V. Monozygous twins with neuromuscular transmission defects at opposite sides of the motor endplate. Acta Neurol Scand 2009, 119:207-211.
125. Riggs K.R., Gutmann L., Riggs J.E. Discordant thymectomy in identical twins concordant for myasthenia gravis. Ann Intern Med 2011, 155:478-479.