Skip to main content

Thymus and Thymoma in Myasthenia Gravis Patients

  • Chapter
The Thymus Gland
  • 916 Accesses

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Sempowski G, Thomasch J, Gooding M, et al. Effect of thymectomy on human peripheral blood T cell pools in myasthenia gravis. J Immunol 2001;166:2808–2817.

    PubMed  CAS  Google Scholar 

  2. Gill J, Malin M, Sutherland J, Gray D, Hollander G, Boyd R. Thymic generation and regeneration. Immunol Rev 2003;195:28–50.

    Article  PubMed  CAS  Google Scholar 

  3. Germain RN. T cell development and the CD4-CD8 lineage decision. Nat Rev Immunol 2002;2:309–322.

    Article  PubMed  CAS  Google Scholar 

  4. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immuno-logical tolerance to self and non-self. Nat Immunol 2005;6:345–352.

    Article  PubMed  CAS  Google Scholar 

  5. Newsom-Davis J, Beeson D. Myasthenia gravis and myasthenic syndromes. In Karpati G, Hilton-Jones D, Griggs R. Disorders of Voluntary Muscle, 7th edn. Cambridge University Press, 2001, pp 650–675.

    Google Scholar 

  6. Engel AG, Ohno K, Sine SM. Sleuthing molecular targets for neurological disease at the neuromuscular junction. Nat Rev Neurosci 2003;4:339–352.

    Article  PubMed  CAS  Google Scholar 

  7. Vincent A. Unravelling the pathogenesis of myasthenia gravis. Nat Rev Immunol 2002;2:797–804.

    Article  PubMed  CAS  Google Scholar 

  8. Vincent A, Drachman DB. Myasthenia gravis. Adv Neurol 2002;88:159–188.

    PubMed  CAS  Google Scholar 

  9. Beeson D, Jacobson L, Newsom-Davis J, Vincent A. A transfected human muscle cell line expressing the adult subtype of the human muscle acetylcholine receptor for diagnostic assays in myasthenia gravis. Neurology 1996;47:1552–1555.

    PubMed  CAS  Google Scholar 

  10. McConville J, Farrugia ME, Beeson D, et al. Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Ann Neurol 2004;55:580–584.

    Article  PubMed  CAS  Google Scholar 

  11. Wirtz PW, Sotodeh M, Nijnuis M, et al. Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiat 2002;73:766–768.

    Article  PubMed  CAS  Google Scholar 

  12. Kubo T, Noda M, Takai T, et al. Primary structure of delta subunit precursor of calf muscle acetylcholine receptor deduced from cDNA sequence. Eur J Biochem 1985;149:5–13.

    Article  PubMed  CAS  Google Scholar 

  13. Tzartos SJ, Barkas T, Cung MT, et al. Anatomy of the antigenic structure of a large membrane autoantigen, the muscle-type nicotinic acetylcholine receptor. Immunol Rev 1998;163:89–120.

    Article  PubMed  CAS  Google Scholar 

  14. Engel AG, Lambert EH, Howard FM. Immune complexes (IgG and C3) at the motor end-plate in myasthenia gravis: ultrastructural and light microscopic localization and electrophysiologic correlations. Mayo Clin Proc 1977;l52:267–280.

    Google Scholar 

  15. Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A. Autoantibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without anti-acetylcholine receptor antibodies. Nature Medicine 2001;7:365–368.

    Article  PubMed  CAS  Google Scholar 

  16. Keynes G. History of myasthenia gravis. Med Hist 1961;5:313–326.

    PubMed  CAS  Google Scholar 

  17. Jaretzki A, Steinglass KM and Sonett JR. Thymectomy in the management of myasthenia gravis. Semin Neurol 2004;24:49–62.

    Article  PubMed  Google Scholar 

  18. Gronseth GS, Barohn RJ. Practice parameter: thymectomy for myasthenia gravis (an evidence-based review). Neurology 2000;55:7–15.

    PubMed  CAS  Google Scholar 

  19. Janer M, Cowland A, Picard J, et al. A susceptibility region for MG extending into the HLA-class I sector telomeric to HLA-C. Human Immunol 1999;60:909–917.

    Article  CAS  Google Scholar 

  20. Roxanis I, Micklem K, Willcox N. Thymic myoid cells and germinal center formation in myasthenia gravis; possible roles in pathogenesis. J Neuroimmunol 2002;125:185–197.

    Article  PubMed  CAS  Google Scholar 

  21. Shiono H, Roxanis I, Zhang W, et al. Scenarios for autoimmunization of T and B cells in myasthenia gravis. Ann N Y Acad Sci 2003;998:237–256.

    Article  PubMed  CAS  Google Scholar 

  22. Meraouna A, Cizeron-Clairac G, Le Panse R, et al. The chemokine CXCL13 is a key molecule in autoimmune Myasthenia Gravis. Blood prepublished online March 16, 2006; DOI 10.1182/blood-2005-06-2383.

    Google Scholar 

  23. Schluep M, Willcox N, Vincent A, Dhoot GK, Newsom-Davis J. Acetylcholine receptors in human thymic myoid cells in situ: an immunohistological study. Ann Neurol 1987;22:212–222.

    Article  PubMed  CAS  Google Scholar 

  24. McHeyzer-Williams LJ, McHeyzer-Williams MG. Antigen-specific memory B cell development. Annu Rev Immunol 2005;23:487–513.

    Article  PubMed  CAS  Google Scholar 

  25. Matthews I, Sims GP, Ledwidge S, Stott DI, Willcox N, Vincent A. Antibodies to human acetylcholine receptor in parous women: evidence for immunization by fetal antigen. Lab Invest 2002;82:1407–1417.

    PubMed  CAS  Google Scholar 

  26. Willcox HN, Newsom-Davis J, Calder LR. Greatly increased autoantibody production in myasthenia gravis by thymocyte suspensions prepared with proteolytic enzymes. Clin Exp Immunol 1983;54:378–386.

    PubMed  CAS  Google Scholar 

  27. Willcox N, Schluep M, Sommer N, et al. Variable corticosteroid sensitivity of thymic cortex and medullary peripheral-type lymphoid tissue in myasthenia gravis patients: structural and functional effects. Quart J Med 1989;73:1071–1087.

    PubMed  CAS  Google Scholar 

  28. Leite MI, Strobel P, Jones M, et al. Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann Neurol 2005;57:444–448.

    Article  PubMed  Google Scholar 

  29. Lauriola L, Ranelletti F, Maggiano N, et al. Thymus changes in anti-MuSK-positive and-negative myasthenia gravis. Neurology 2005;64:536–538.

    PubMed  CAS  Google Scholar 

  30. Evoli A, Tonali PA, Padua L. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain 2003;126:2304–2311.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  32. Steinmann GG, Klaus B, Muller-Hermelink HK. The involution of the ageing human thymic epithelium is independent of puberty: a morphometric study. Scand J Immunol 1985;22:563–575.

    Article  PubMed  CAS  Google Scholar 

  33. Giraud M, Beaurain G, Yamamoto AM, et al. Linkage of HLA to myasthenia gravis and genetic heterogeneity depending on anti-titin antibodies. Neurology 2001;57:1555–1560.

    PubMed  CAS  Google Scholar 

  34. Kondo K, Monden Y. Thymoma and myasthenia gravis: a clinical study of 1,089 patients from Japan. Ann Thorac Surg 2005;79:219–224.

    Article  PubMed  Google Scholar 

  35. Souadjian JV, Enriquez P, Silverstein MN, Pepin JM. The spectrum of diseases associated with thymoma: coincidence or syndrome? Arch Int Med 1974;134:374–379.

    Article  CAS  Google Scholar 

  36. Namba T, Brunner NG, Grob D. Myasthenia gravis in patients with thymoma, with particular reference to onset after thymectomy. Medicine (Baltimore) 1978;57:411–433.

    Article  PubMed  CAS  Google Scholar 

  37. Aarli JA, Stefansson K, Marton LS, Wollmann RL. Patients with myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin. Clin Exp Immunol 1990;82:284–288.

    Article  PubMed  CAS  Google Scholar 

  38. Mygland A, Tysnes OB, Matre R, Volpe P, Aarli JA, Gilhus NE. Ryanodine receptor autoantibodies in myasthenia gravis patients with a thymoma. Ann Neurol 1992;32:589–591.

    Article  PubMed  CAS  Google Scholar 

  39. Meager A, Wadhwa M, Dilger P, et al. Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis. Clin Exp Immunol 2003;132:128–136.

    Article  PubMed  CAS  Google Scholar 

  40. Buckley C, Newsom-Davis J, Willcox N, Vincent A. Do titin and cytokine antibodies in MG patients predict thymoma or thymoma recurrence? Neurology 2001;57:1579–1582.

    PubMed  CAS  Google Scholar 

  41. Rosai J, Levine GD. Tumors of the thymus. In Atlas of tumor pathology. US Armed Forces Institute of Pathology, Washington, DC, 1976, 2nd Series, Fascicle 13.

    Google Scholar 

  42. Inoue M, Starostik P, Zettl A, et al. Correlating genetic aberrations with World Health Organization-defined histology and stage across the spectrum of thymomas. Cancer Res 2003;63:3708–3715.

    PubMed  CAS  Google Scholar 

  43. Marx A, Müller-Hermelink H. From basic immunobiology to the upcoming WHO-classification of tumors and the thymus. Path Res Practice 1999;195:515–533.

    CAS  Google Scholar 

  44. Chen G, Marx A, Wen-Hu C, et al. New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China. Cancer 2002;95:420–429.

    Article  PubMed  Google Scholar 

  45. Kim DJ, Yang WI, Choi SS, Kim KD, Chung KY. Prognostic and clinical relevance of the World Health Organization schema for the classification of thymic epithelial tumors: a clinicopathologic study of 108 patients and literature review. Chest 2005;127:755–761.

    Article  PubMed  Google Scholar 

  46. Willcox N, Schluep M, Ritter MA, Schuurman HJ, Newsom-Davis J, Christensson B. Myasthenic and nonmyasthenic thymoma. An expansion of a minor cortical epithelial cell subset? Am J Pathol 1987;127:447–460.

    PubMed  CAS  Google Scholar 

  47. Buckley C, Douek D, Newsom-Davis J, Vincent A, Willcox N. Mature, long-lived CD4+ and CD8+ T cells are generated by thymomas in myasthenia gravis. Ann Neurol 2001;50:64–72.

    Article  PubMed  CAS  Google Scholar 

  48. Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981;48:2485–2492.

    Article  PubMed  CAS  Google Scholar 

  49. Verley JM, Hollmann KH. Thymoma. A comparative study of clinical stages, histologic features, and survival in 200 cases. Cancer 1985;55:1074–1086.

    Article  PubMed  CAS  Google Scholar 

  50. Kondo K, Yoshizawa K, Tsuyuguchi M, et al. WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg 2004;77:1183–1188.

    Article  PubMed  Google Scholar 

  51. Kesler KA, Wright CD, Loehrer PJ. Thymoma: current medical and surgical management. Semin Neurol 2004;24:63–73.

    Article  PubMed  Google Scholar 

  52. Giaccone G. Treatment of malignant thymoma. Curr Opin Oncol 2005;17:140–146.

    Article  PubMed  Google Scholar 

  53. Loehrer PJ Sr, Wang W, Johnson DH, Aisner SC, Ettinger DS. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group Phase II Trial. J Clin Oncol 2004;22:293–299.

    Article  PubMed  CAS  Google Scholar 

  54. Willcox N. Myasthenia gravis. Curr Opin Immunol 1993;5:910–917.

    Article  PubMed  CAS  Google Scholar 

  55. Kuo T, Shih LY. Histologic types of thymoma associated with pure red cell aplasia: a study of five cases including a composite tumor of organoid thymoma associated with an unusual lipofibroadenoma. Int J Surg Pathol 2001;9:29–35.

    PubMed  CAS  Google Scholar 

  56. Kadota Y, Okumura M, Miyoshi S, et al. Altered T cell development in human thymoma is related to impairment of MHC class II transactivator expression induced by interferon-gamma (IFN-gamma). Clin Exp Immunol 2000;121:59–68.

    Article  PubMed  CAS  Google Scholar 

  57. Siara J, Rudel R, Marx A. Absence of acetylcholine-induced current in epithelial cells from thymus glands and thymomas of myasthenia gravis patients. Neurology 1991;41:128–131.

    PubMed  CAS  Google Scholar 

  58. Nagvekar N, Moody AM, Moss P, et al. A pathogenetic rôle for the thymoma in myasthenia gravis; autosensitization of IL4-producing T cell clones recognising extracellular AChR epitopes presented by minority class II isotypes. J Clin Invest 1998;101:2268–2277.

    PubMed  CAS  Google Scholar 

  59. Vincent A, Palace J and Hilton-Jones D. Myasthenia gravis. Lancet 2001;357:212–218.

    Article  Google Scholar 

  60. Palace J, Vincent A, Beeson D. Myasthenia gravis: diagnostic and management dilemmas. Curr Opin Neurol 2001;14:583–589.

    Article  PubMed  CAS  Google Scholar 

  61. Richman DP, Agius M. Treatment of autoimmune myasthenia gravis. Neurology 2003;61:1652–1661.

    PubMed  CAS  Google Scholar 

  62. Newsom-Davis J. Therapy in MG and Lambert-Eaton myasthenic syndrome. Semin Neurol 2003;23:191–198.

    Article  PubMed  Google Scholar 

  63. Riemersma S, Vincent A, Beeson D, et al. Association of arthrogryposis multiplex congenita with maternal antibodies inhibiting fetal acetylcholine receptor function. J Clin Invest 1996;98:2358–2363.

    Article  PubMed  CAS  Google Scholar 

  64. O’Neill JH, Murray NM, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome. A review of 50 cases. Brain 1988;111:577–596.

    Article  PubMed  Google Scholar 

  65. Lang B, Newsom-Davis J, Wray D, Vincent A and Murray N. Autoimmune aetiology for the myasthenic (Eaton-Lambert) syndrome. Lancet 1981;2:224–226.

    Article  PubMed  CAS  Google Scholar 

  66. Pinto A, Iwasa K, Newland C, Newsom-Davis J, Lang B. The action of Lambert-Eaton myasthenic syndrome immunoglobulin G on cloned human voltage-gated calcium channels. Muscle & Nerve 2002;25:715–724.

    Article  CAS  Google Scholar 

  67. Motomura M, Johnston I, Lang B, Vincent A, Newsom-Davis J. An improved diagnostic assay for Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiat 1995;58:85–87.

    Article  PubMed  CAS  Google Scholar 

  68. Roberts A, Perera S, Lang B, Vincent A, Newsom-Davis J. Paraneoplastic myasthenic syndrome IgG inhibits 45Ca2+ flux in a human small cell carcinoma line. Nature 1985;317:737–739.

    Article  PubMed  CAS  Google Scholar 

  69. Chalk CH, Murray NM, Newsom-Davis J, O’Neill JH, Spiro SG. Response of the Lambert-Eaton myasthenic syndrome to treatment of associated small-cell lung carcinoma. Neurology 1990;40:1552–1556.

    PubMed  CAS  Google Scholar 

  70. Maddison P, Newsom-Davis J, Mills KR, Souhami, RL Favourable prognosis in the Lambert-Eaton myasthenic syndrome and small cell lung carcinoma. Lancet 1999;353:117–118.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Willcox, N. (2007). Thymus and Thymoma in Myasthenia Gravis Patients. In: Anastasiadis, K., Ratnatunga, C. (eds) The Thymus Gland. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-33426-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-33426-2_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-33425-5

  • Online ISBN: 978-3-540-33426-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics