A CTLA4high genotype is associated with myasthenia gravis in thymoma patients.

Chuang, Wen-Yu; Ströbel, Philipp; Gold, Ralf; Nix, Wilfred; Schalke, Berthold; Kiefer, Reinhard; Opitz, Andreas; Klinker, Erdwine et al. · Ann Neurol · 2005

case_control · Level III

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Abstract

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.

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