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The HLA-B*4601-DRB1*0901 haplotype is positively correlated with juvenile ocular myasthenia gravis in a southern Chinese Han population

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Abstract

Myasthenia gravis (MG) is a sporadic disorder that has been increasingly linked to inherited genetic factors. Previous studies have demonstrated that human leukocyte antigen (HLA) plays an important role in the pathogenesis of MG. We determined the genotypes of the HLA-A, B, and DRB1 alleles in 257 southern Chinese Han MG patients using polymerase chain reaction sequence-based typing (PCR-SBT). The allele frequencies in the MG patients were compared to 292 healthy controls using the case–control method. HLA-A*0207, HLA-B*4601, HLA-DRB1*0403, HLA-DRB1*0901, and HLA-DRB1*1602 were more frequent in juvenile ocular MG patients than controls. HLA-DRB1*0701 was significantly reduced in the juvenile ocular MG group compared with controls. HLA-A*0207-B*4601, HLA-B*4601-DRB1*0403, HLA-B*4601-DRB1*0901, and HLA-B*4601-DRB1*1602 were found to be in strong linkage disequilibrium in juvenile ocular MG patients. Within the MG patients, there was a strong positive association between HLA-B*4601-DRB1*0901 and juvenile ocular MG patients, and the value of odds ratios (OR) decreased as the disease became more severe and the age of onset increased. We believe this could be the main heredity phenotype in juvenile ocular MG patients from southern China and may be a clinical marker to predict the severity of the disease.

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References

  1. Kerty E, Elsais A, Argov Z et al (2014) EFNS/ENS guidelines for the treatment of ocular myasthenia. Eur J Neurol 21(5):687–693

    Article  CAS  PubMed  Google Scholar 

  2. Berrih-Aknin S, Frenkian-Cuvelier M, Eymard B (2014) Diagnostic and clinical classification of autoimmune myasthenia gravis. J Autoimmun 48–49:143–148

    Article  PubMed  Google Scholar 

  3. Gilhus NE (2009) Autoimmune myasthenia gravis. Expert Rev Neurother 9(3):351–358

    Article  CAS  PubMed  Google Scholar 

  4. Li F, Szobor A, Croxen R et al (2001) Dominantly inherited familial myasthenia gravis as a separate genetic entity without involvement of defined candidate gene loci. Int J Mol Med 7(3):289–294

    CAS  PubMed  Google Scholar 

  5. Lee BW, Ihm SH, Shin HS et al (2008) Malignant thymoma associated with myasthenia gravis, Graves’ disease, and SIADH. Inter Med 47(11):1009–1012

    Article  Google Scholar 

  6. Murai H (2014) Myasthenia gravis: past, present and future. Rinsho Shinkeigaku 54(12):947–949

    Article  PubMed  Google Scholar 

  7. Feng HY, Liu WB, Luo CM et al (2012) A retrospective review of 15 patients with familial myasthenia gravis over a period of 25 years. Neurol Sci 33(4):771–777

    Article  PubMed  Google Scholar 

  8. Saint-Faust M, Perelman S, Dupont D et al (2010) Transient neonatal myasthenia gravis revealing a myasthenia gravis and a systemic lupus erythematosus in the mother: case report and review of the literature. Am J Perinatol 27(2):107–110

    Article  PubMed  Google Scholar 

  9. Kerzin-Storrar L, Metcalfe RA, Dyer PA et al (1988) Genetic factors in myasthenia gravis: a family study. Neurology 38(1):38–42

    Article  CAS  PubMed  Google Scholar 

  10. Provenzano C, Arancio O, Evoli A et al (1988) Familial autoimmune myasthenia gravis with different pathogenetic antibodies. J Neurol Neurosurg Psychiatry 51(9):1228–1230

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Huang X, Liu WB, Men LN et al (2013) Clinical features of myasthenia gravis in southern China: retrospective review of 2154 cases over 22 years. Neurol Sci 34(6):911–917

    Article  CAS  PubMed  Google Scholar 

  12. Deitiker PR, Oshima M, Smith RG et al (2011) Association with HLA DQ of early onset myasthenia gravis in Southeast Texas region of the United States. Int J Immunogenet 38(1):55–62

    Article  CAS  PubMed  Google Scholar 

  13. van Lith M, McEwen-Smith RM, Benham AM (2010) HLA-DP, HLA-DQ, and HLA-DR have different requirements for invariant chain and HLA-DM. J Biol Chem 285(52):40800–40808

    Article  PubMed Central  PubMed  Google Scholar 

  14. Iwasa K, Kato-Motozaki Y, Furukawa Y et al (2010) Up-regulation of MHC class I and class II in the skeletal muscles of myasthenia gravis. J Neuroimmunol 225(1–2):171–174

    Article  CAS  PubMed  Google Scholar 

  15. Xie YC, Qu Y, Sun L et al (2011) Association between HLA-DRB1 and myasthenia gravis in a northern Han Chinese population. J Clin Neurosci 18(11):1524–1527

    Article  CAS  PubMed  Google Scholar 

  16. Nikolic AV, Andric ZP, Simonovic RB et al (2015) High frequency of DQB1*05 and absolute absence of DRB1*13 in muscle-specific tyrosine kinase positive myasthenia gravis. Eur J Neurol 22(1):59–63

    Article  CAS  PubMed  Google Scholar 

  17. Bartoccioni E, Scuderi F, Augugliaro A et al (2009) HLA class II allele analysis in MuSK-positive myasthenia gravis suggests a role for DQ5. Neurology 72(2):195–197

    Article  CAS  PubMed  Google Scholar 

  18. Deitiker PR, Oshima M, Smith RG et al (2006) Subtle differences in HLA DQ haplotype-associated presentation of AChR alpha-chain peptides may suffice to mediate myasthenia gravis. Autoimmunity 39(4):277–288

    Article  CAS  PubMed  Google Scholar 

  19. Alahgholi-Hajibehzad M, Yilmaz V, Gülsen-Parman Y et al (2013) Association of HLA-DRB1*14, -DRB1*16 and -DQB1*05 with MuSK-myasthenia gravis in patients from Turkey. Hum Immunol 74(12):1633–1635

    Article  CAS  PubMed  Google Scholar 

  20. Niks EH, Kuks JB, Roep BO et al (2006) Strong association of MuSK antibody-positive myasthenia gravis and HLA-DR14-DQ5. Neurology 66(11):1772–1774

    Article  CAS  PubMed  Google Scholar 

  21. Marino M, Maiuri MT, Di Sante G et al (2014) T cell repertoire in DQ5-positive MuSK-positive myasthenia gravis patients. J Autoimmun 52:113–121

    Article  CAS  PubMed  Google Scholar 

  22. Yousefipour GA, Salami Z, Farjadian S (2009) Association of HLA-DQA1*0101/2 and DQB1*0502 with myasthenia gravis in southern Iranian patients. Iran J Immunol 6(2):99–102

    CAS  PubMed  Google Scholar 

  23. Jaretzki A 3rd, Barohn RB, Ernstoff RM et al (2000) Myasthenia gravis. Recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 55(1):16–23

    Article  PubMed  Google Scholar 

  24. Stojkovic T, Behin A (2010) Ocular myasthenia: diagnosis and treatment. Rev Neurol 166(12):987–997

    Article  CAS  PubMed  Google Scholar 

  25. Zach H, Cetin H, Hilger E et al (2013) The effect of early prednisolone treatment on generalization. Eur J Neurol 20(4):708–713

    Article  CAS  PubMed  Google Scholar 

  26. Angelini C (2011) Diagnosis and management of autoimmune myasthenia gravis. Clin Drug Investig 3(1):1–14

    Article  Google Scholar 

  27. Hellmann MA, Mosberg-Galili R, Steiner I (2013) Myasthenia gravis in the elderly. J Neurol Sci 325(1–2):1–5

    Article  PubMed  Google Scholar 

  28. Segawa M (1973) Myasthenia gravis—latent general type. Naika 31:1222–1226

    Google Scholar 

  29. Shinomiya N, Nomura Y, Segawab M (2004) A variant of childhood-onset myasthenia gravis: HLA typing and clinical characteristics in Japan. Clin Immunol 110(2):154–158

    Article  CAS  PubMed  Google Scholar 

  30. Cheng C, Liu Z, Xu F et al (2013) Clinical outcome of juvenile myasthenia gravis after extended transsternal thymectomy in a Chinese cohort. Ann Thorac Surg 95(3):1035–1041

    Article  PubMed  Google Scholar 

  31. Wang H, Su Z, Luo C et al (2013) The effect of steroid treatment and thymectomy on bone age and height development in juvenile myasthenia gravis. Neurol Sci 34(12):2173–2180

    Article  PubMed  Google Scholar 

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The authors declare that there is no conflict of interest regarding the publication of this paper.

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Correspondence to Wei-bin Liu.

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H. Feng and L. Yang contributed equally to this work.

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Feng, Hy., Yang, Lx., Liu, Wb. et al. The HLA-B*4601-DRB1*0901 haplotype is positively correlated with juvenile ocular myasthenia gravis in a southern Chinese Han population. Neurol Sci 36, 1135–1140 (2015). https://doi.org/10.1007/s10072-015-2235-9

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