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A CTLA4 high genotype is associated with myasthenia gravis in thymoma patients
Author(s) -
Chuang WenYu,
Ströbel Philipp,
Gold Ralf,
Nix Wilfred,
Schalke Berthold,
Kiefer Reinhard,
Opitz Andreas,
Klinker Erdwine,
MüllerHermelink Hans K.,
Marx Alexander
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20577
Subject(s) - thymoma , myasthenia gravis , genotype , immunology , autoimmune disease , medicine , pathogenesis , cytotoxic t cell , disease , thymectomy , antigen , pathology , gene , biology , genetics , in vitro
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 CTLA4 high 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 CTLA4 high 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. Ann Neurol 2005;58:644–648
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