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RESEARCH PRODUCT
A CTLA4high genotype is associated with myasthenia gravis in thymoma patients
Wen-yu ChuangWen-yu ChuangHans K. Müller-hermelinkAndreas OpitzWilfred NixBerthold SchalkeRalf GoldRalf GoldReinhard KieferErdwine KlinkerPhilipp StröbelAlexander Marxsubject
AdultMaleThymomaAdolescentGenotypeThymomaDisease Associationchemical and pharmacologic phenomenaPolymorphism Single NucleotidePathogenesis03 medical and health sciences0302 clinical medicineGene FrequencyAntigenAntigens CDhemic and lymphatic diseasesMyasthenia GravisGenotypeHumansMedicineCytotoxic T cellCTLA-4 AntigenChildGeneAgedDemography030304 developmental biology0303 health sciencesbusiness.industryThymus NeoplasmsMiddle Agedmedicine.diseaseAntigens DifferentiationMyasthenia gravis3. Good healthNeurologyImmunologyFemaleNeurology (clinical)business030215 immunologydescription
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. Ann Neurol 2005;58:644–648
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2005-09-24 | Annals of Neurology |