Thymomas Express Ryanodine Receptor Epitopes

  • Åse Mygland
  • Goro Kuwajima
  • Katsuhiko Mikoshiba
  • Johan A. Aarli
  • Nils Erik Gilhus


Myasthenia gravis (MG) patients with thymoma have antibodies against the Ca2+release channel of striated muscle, the ryanodine receptor (RyR). Thymomas were examined for immunoreactivity with a panel of polyclonal antibodies against RyR peptides. An antibody raised against a peptide in the transmembrane segment of cardiac and skeletal muscle RyR immunostained thymoma epitehlial cells in sections of 17/23 thymomas, and detected a 40 kDa peptide in membrane fractions of thymoma. The RyR peptide was not detected in normal thymus, tonsil or carcinoma of colon. The results indicate that neoplastic thymoma cells express epitopes shared by skeletal and cardiac muscle RyR.


Ryanodine Receptor Normal Thymus Neoplastic Epithelial Cell Thymoma Patient Slow Skeletal Muscle Fiber 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lewis JE, Wick MR, Scheithauer BW, Bernatz PE, Taylor WF. Thymoma. A clinicopathologic review. Cancer 1987:60:2727–2743.PubMedCrossRefGoogle Scholar
  2. 2.
    Mygland Å, Tysnes O-B, Matre R, Volpe P, Aarli JA, Gilhus NE. Ryanodine receptor autoantibodies in myasthenia gravis patients with a thymoma. Ann Neurol 1992:32:589–591.PubMedCrossRefGoogle Scholar
  3. 3.
    Aarli JA, Stefansson K, Marton LSG, Wollmann RL. Patients with myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin. Clin Exp Immunol 1990:82:284–288.PubMedCrossRefGoogle Scholar
  4. 4.
    Gautel M, Lakey A, Barlow DP, Holmes Z, Scales S, Leonard K, Labeit S, Mygland Å, Gilhus NE, Aarli JA. Titin antibodies in myasthenia gravis; identification of a major immunogenic region of titin. Neurology 1993:43:1581–1585.PubMedCrossRefGoogle Scholar
  5. 5.
    Williams CL, Lennon VA. Thymic B lymphocyte clones from patients with myosin, alpha-actinin, or actin. J Exp Med 1986:164:1043–1059.PubMedCrossRefGoogle Scholar
  6. 6.
    Mygland Å, Tysnes O-B, Aarli JA, Flood PR, Gilhus NE. Myasthenia gravis patients with a thymoma have antibodies against a high molecular weight protein in sarcoplasmic reticulum. J Neurotmmunol 1992:37:1–7.CrossRefGoogle Scholar
  7. 7.
    Otsu K, Willard HF, Khanna VK, Zorzato F, Green NM, MacLennan DH. Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum. J Biol Chem 1990:265:13472–13483.PubMedGoogle Scholar
  8. 8.
    McPherson PS, Campbell KP. The ryanodine receptor/Ca2+ release channel. J Biol Chem 1993:268:13765–13768.PubMedGoogle Scholar
  9. 9.
    Mygland Å, Aarli JA., Matre R, Gilhus NE. Ryanodine receptor antibodies related to severity of thymoma-associated myasthenia gravis. J Neurol Neurosurg Psychiat 1994:57:843–846.PubMedCrossRefGoogle Scholar
  10. 10.
    Boyd RL, Tucek TL, Godfrey DI, Izon DJ, Wilson TJ, Davidson NJ, Bean AGD, Ladyman HM, Ritter MA, Hugo P. The thymic microenvironment. Immunol Today. 1993:14:445–459.PubMedCrossRefGoogle Scholar
  11. 11.
    Gilhus NE, Aarli JA, Christensson B, Matre R. Rabbit antiserum to a citric acid extract of human skeletal muscle staining thymomas from myasthenia gravis patients. J Neuroimmunol 1984/85:7:55-64.Google Scholar
  12. 12.
    Marx A, O’Connor R, Geuder KI, Hoppe F, Schalke B, Tzartos S, Kalies I, Kirchner T, Müller-Hermelink, H.K. Characterization of a protein with an acetylcholine receptor epitope from myasthenia gravis-associated thymomas. Lab Invest 1990:62:279–286.PubMedGoogle Scholar
  13. 13.
    Dardenne M, Savino W and Bach J-F. Thymomatous epithelial cells and skeletal muscle share a common epitope defined by a monoclonal antibody. Am J Pathol 1987:126:194–198.PubMedGoogle Scholar
  14. 14.
    Gilhus NE, Willcox N, Harcourt G, Nagvekar N, Beeson D, Vincent A, Newsom-Davis J. Antigen presentation by thymoma epithelial cells from myasthenia gravis patients to potentially pathogenic T cells. J Neuroimmunol 1995:56:65–76.PubMedCrossRefGoogle Scholar
  15. 15.
    Takeshima H, Nishimura S, Matsumoto T, Ishida H, Kangawa K, Minamino N, Matsuo H, Ueda M, Hanaoka M, Hirose T, Numa S. Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor. Nature 1989:339:439–445.PubMedCrossRefGoogle Scholar
  16. 16.
    Kuwajima G, Futatsugi A, Niinobe M, Nakanishi N, Mikoshiba K. Two types of ryanodine receptors in mouse brain: skeletal muscle type exclusively in Purkinje cells and cardiac muscle type in various neurons. Neuron 1992:9:1133–1142.PubMedCrossRefGoogle Scholar
  17. 17.
    Jones LR, Besch HR Jr, Fleming JW, McConnaughey MM, Watanabe AM. Separation of vesicles of cardiac sarcolemma from vesicles of cardiac sarcoplasmic reticulum: comparative biochemical analysis of component activities. J Biol Chem 1979:254:530–539.Google Scholar
  18. 18.
    Towbin H, Stahelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci. USA 1979:76:4350–4354.CrossRefGoogle Scholar
  19. 19.
    Mygland A, Tysnes O-B, Matre R, Aarli JA, Gilhus NE. Anti-cardiac ryanodine receptor antibodies in thymoma-associated mysthenia gravis. Autoimmunity 1994:17:327–331.PubMedCrossRefGoogle Scholar
  20. 20.
    Imagawa T, Takasago T, Shigekawa M. Cardiac ryanodine receptor is absent in type 1 slow skeletal muscle fibers: immunochemical and ryanodine binding studies. J Biochem 1989:342-348.Google Scholar
  21. 21.
    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.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Åse Mygland
    • 1
  • Goro Kuwajima
    • 2
  • Katsuhiko Mikoshiba
    • 3
  • Johan A. Aarli
    • 4
  • Nils Erik Gilhus
    • 4
  1. 1.Department of NeurologyVest-Agder Central HospitalKristiansandNorway
  2. 2.Shinogi Institute for Medical ScienceOsakaJapan
  3. 3.Tokyo UniversityTokyoJapan
  4. 4.Department of NeurologyUniversity of BergenBergenNorway

Personalised recommendations