0000000000436023
AUTHOR
Reinhard Kiefer
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…
The ageing and myasthenic thymus: a morphometric study validating a standard procedure in the histological workup of thymic specimens.
The thymus is believed to play an important role in the pathogenesis of myasthenia gravis (MG). The 80% of MG patients with anti-acetylcholine receptor autoantibodies fall into three clinical subgroups: 1) thymoma; 2) early-onset MG (<age of 40; EOMG) and 3) late-onset (LOMG; onset after 40). Thymectomy is widely used in EOMG, but its benefits have not been established in randomized controlled trials. A multicenter international trial (MGTX) currently seeks to determine whether thymectomy reduces corticosteroid requirements, and to look for correlations with thymic histology. We here describe the validated, standardized histological workup and reporting system used in this trial.
Selective loss of regulatory T cells in thymomas
Myasthenia gravis (MG) is the prime autoimmune manifestation of thymomas. We investigated the generation of T cells with a regulatory phenotype (T(R)) in thymomas with and without associated MG. In patients with MG(+) thymomas, maturation and export of T(R) cells but not of other T-cell subsets was significantly reduced. We conclude that imbalance between effector and regulatory T cells in thymomas may be involved in modulation of onset and/or severity of MG.