Surgery Today

, Volume 43, Issue 5, pp 461–466 | Cite as

The thymus, thymoma and myasthenia gravis

  • Yoshitaka FujiiEmail author
Review Article


Myasthenia gravis is an autoimmune disease. An autoantibody directed toward acetylcholine receptor (AChR) causes the destruction of the postsynaptic membrane and a reduction of the number of AChRs at neuromuscular junctions. A very puzzling, but interesting characteristic of myasthenia gravis is that many of the patients have an abnormality in their thymus. Many have a hyperplastic thymus with germinal centers, while others have a thymic tumor. How is the abnormality of the thymus related to myasthenia gravis? This review will summarize the existing evidence and try to find the missing link between the thymus and myasthenia gravis. The review will also comment on two distinct populations of myasthenia gravis patients without thymoma. The autoimmunity found in elderly patients is nonspecific and initiated via a different mechanism from the initiation of myasthenia gravis in younger patients.


Autoantibody Autoimmune disease T cell development in thymoma Graft-versus-host disease Neuromuscular transmission 


Conflict of interest

The author has no conflicts of interest to declare.


  1. 1.
    Ohata N, Usami N, Kawaguchi K, Tateyama H, Yokoi K. Type AB thymoma with brain metastasis: report of a case. Surg Today. 2011;41:1436–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Okumura M, Miyoshi S, Fujii Y, Takeuchi Y, Shiono H, Inoue M, et al. Clinical and functional significance of WHO classification on human thymic epithelial neoplasms: a study of 146 consecutive tumors. Am J Surg Pathol. 2001;25:103–10.PubMedCrossRefGoogle Scholar
  3. 3.
    Lindstrom J, Shelton D, Fujii Y. Myasthenia gravis. Adv Immunol. 1988;42:233–84.PubMedCrossRefGoogle Scholar
  4. 4.
    Okumura M, Fujii Y, Shiono H, Inoue M, Minami M, Utsumi T, Kadota Y, Sawa Y. Immunological function of thymoma and pathogenesis of paraneoplastic myasthenia gravis. Gen Thorac Cardiovasc Surg. 2008;56:143–50.PubMedCrossRefGoogle Scholar
  5. 5.
    Zuklys S, Balciunaite G, Agarwal A, FaslerKan E, Palmer E, Hollander GA. Normal thymic architecture and negative selection are associated with Aire expression, the gene defective in the autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). J Immunol. 2000;165:1976–83.PubMedGoogle Scholar
  6. 6.
    Buckley C, Douek D, NewsomDavis J, Vincent A, Willcox N. Mature, long-lived CD4(+) and CD8(+) T cells are generated by the thymoma in myasthenia gravis. Ann Neurol. 2001;50:64–72.PubMedCrossRefGoogle Scholar
  7. 7.
    Grau JM, Casademont J, Monforte R, Marin P, Granena A, Rozman C, Urbano-Marquez A. Myasthenia gravis after allogeneic bone marrow transplantation: report of a new case and pathogenetic considerations. Bone Marrow Transplant. 1990;5:435–7.PubMedGoogle Scholar
  8. 8.
    Nakagiri T, Okumura M, Inoue M, Minami M, Kiyohara E, Umegaki N, Nakamura T, Tomita Y, Katayama I, Aozasa K. Thymoma-associated graft-versus-host disease-like erythroderma. J Thorac Oncol. 2007;2:1130–2.PubMedCrossRefGoogle Scholar
  9. 9.
    Vernino S, Lennon VA. Autoantibody profiles and neurological correlations of thymoma. Clin Cancer Res. 2004;10:7270–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Villasenor J, Besse W, Benoist C, Mathis D. Ectopic expression of peripheral-tissue antigens in the thymic epithelium: probabilistic, monoallelic, misinitiated. Proc Natl Acad Sci USA. 2008;105:15854–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Suzuki E, Kobayashi Y, Yano M, Fujii Y. Infrequent and low AIRE expression in thymoma: difference in AIRE expression among WHO subtypes does not correlate with association of MG. Autoimmunity. 2008;41:377–82.PubMedCrossRefGoogle Scholar
  12. 12.
    Suzuki S, Utsugisawa K, Yoshikawa H, Motomura M, Matsubara S, Yokoyama K, Nagane Y, Maruta T, Satoh T, Sato H, Kuwana M, Suzuki N. Autoimmune targets of heart and skeletal muscles in myasthenia gravis. Arch Neurol. 2009;66:1334–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Hoch W, McConville J, Helms S, NewsomDavis J, Melms A, Vincent A. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nature Med. 2001;7:365–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Fujii Y, Monden Y, Nakahara K, Hashimoto Y, Kawashima Y. Antibody to acetylcholine receptor in myasthenia gravis: production by lymphocytes from thymus or thymoma. Neurology. 1984;34:1182–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Sims GP, Shiono H, Willcox N, Stott DI. Somatic hypermutation and selection of B cells in thymic germinal centers responding to acetylcholine receptor in myasthenia gravis. J Immunol. 2001;167:1935–44.PubMedGoogle Scholar
  16. 16.
    Hill ME, Shiono H, Newsom-Davis J, Willcox N. The myasthenia gravis thymus: a rare source of human autoantibody-secreting plasma cells for testing potential therapeutics. J Neuroimmunol. 2008;201–202:50–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Fujii Y, Hashimoto J, Monden Y, Ito T, Nakahara K, Kawashima Y. Specific activation of lymphocytes against acetylcholine receptor in the thymus in myasthenia gravis. J Immunol. 1986;136:887–91.PubMedGoogle Scholar
  18. 18.
    Nicolle MW. Pseudo-myasthenia gravis and thymic hyperplasia in Graves’ disease. Can J Neurol Sci. 1999;26:201–3.PubMedGoogle Scholar
  19. 19.
    Nakajima J, Murakawa T, Fukami T, Sano A, Takamoto S, Ohtsu H. Postthymectomy myasthenia gravis: relationship with thymoma and antiacetylcholine receptor antibody. Ann Thorac Surg. 2008;86:941–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Yamamoto AM, Gajdos P, Eymard B, Tranchant C, Warter JM, Gomez L, Bourquin C, Bach JF, Garchon HJ. Anti-titin antibodies in myasthenia gravis: tight association with thymoma and heterogeneity of nonthymoma patients. Arch Neurol. 2001;58:885–90.PubMedCrossRefGoogle Scholar
  21. 21.
    Somnier FE, Engel PJH. The occurrence of anti-titin antibodies and thymomas—a population survey of MG 1970–1999. Neurology. 2002;59:92–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Vincent A, Clover L, Buckley C, Evans JG, Rothwell PM. Evidence of underdiagnosis of myasthenia gravis in older people. J Neurol Neurosurg Psychiatry. 2003;74:1105–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Berer K, Mues M, Koutrolos M, Rasbi ZA, Boziki M, Johner C, Wekerle H, Krishnamoorthy G. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479:538–41.PubMedCrossRefGoogle Scholar
  24. 24.
    Melms A, Malcherek G, Gern U, Wietholter H, Muller CA, Schopfer R, Lindstrom J. T cells from normal and myasthenic individuals recognize the human acetylcholine receptor: heterogeneity of antigenic sites on the alpha-subunit. Ann Neurol. 1992;31:311–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2012

Authors and Affiliations

  1. 1.Department of Oncology, Immunology, and SurgeryNagoya City University Graduate School of Medical SciencesNagoyaJapan

Personalised recommendations