A CTLA4high genotype is associated with myasthenia gravis in thymoma patients.
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.
Chuang
Wen-Yu
WY
Institute of Pathology, University of Würzburg, Würzburg, Germany.
Ströbel
Philipp
P
Gold
Ralf
R
Nix
Wilfred
W
Schalke
Berthold
B
Kiefer
Reinhard
R
Opitz
Andreas
A
Klinker
Erdwine
E
Müller-Hermelink
Hans K
HK
Marx
Alexander
A
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*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human