title: A CTLA4high genotype is associated with myasthenia gravis in thymoma patients.
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.
authors.affiliation: Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Chuang
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.forename: Wilfred
authors.initials: W
authors.lastname: Nix
authors.forename: Berthold
authors.initials: B
authors.lastname: Schalke
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kiefer
authors.forename: Andreas
authors.initials: A
authors.lastname: Opitz
authors.forename: Erdwine
authors.initials: E
authors.lastname: Klinker
authors.forename: Hans K
authors.initials: HK
authors.lastname: Müller-Hermelink
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics* / Q000378:metabolism; D060908:CTLA-4 Antigen; D002648:Child; D003710:Demography; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013945:Thymoma / Q000150:complications*; D013953:Thymus Neoplasms / Q000150:complications / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human