A CTLA4high genotype is associated with myasthenia gravis in thymoma patients

Ann Neurol. 2005 Oct;58(4):644-8. doi: 10.1002/ana.20577.


Myasthenia gravis (MG) in thymoma patients depends critically on intratumorous generation and export of mature autoreactive CD4+ T cells. Why non-MG thymomas fail to produce CD4+ T cells is unknown. We studied three single-nucleotide polymorphisms of the cytotoxic T-lymphocyte-associated antigen 4(CTLA4) gene in thymoma patients, nonthymoma early-onset MG patients, and control subjects. Surprisingly, the CTLA4high genotype +49A/A, which is protective against several autoimmune diseases, exerted a prominent predisposing effect to paraneoplastic MG in thymoma patients. The unusual disease association with a CTLA4high genotype implies a unique pathogenesis of paraneoplastic MG, with high CTLA4 levels possibly supporting the nontolerogenic selection of CD4+ T cells in MG-associated thymomas.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD
  • Antigens, Differentiation / genetics*
  • Antigens, Differentiation / metabolism
  • CTLA-4 Antigen
  • Child
  • Demography
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Myasthenia Gravis / etiology
  • Myasthenia Gravis / genetics*
  • Polymorphism, Single Nucleotide
  • Thymoma / complications*
  • Thymus Neoplasms / complications
  • Thymus Neoplasms / genetics*


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human