Kanatli Irem, Akkaya Bahar, Uysal Hilmi, Kahraman Sevim, Sanlioglu Ahter Dilsad
Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, 07058, Antalya, Turkey; Center for Gene and Cell Therapy, Akdeniz University, 07058 Antalya, Turkey.
Department of Pathology, Faculty of Medicine, Akdeniz University, 07058 Antalya, Turkey.
Neuromuscul Disord. 2017 Feb;27(2):128-135. doi: 10.1016/j.nmd.2016.10.012. Epub 2016 Nov 4.
Myasthenia Gravis is an autoantibody-mediated, neuromuscular junction disease, and is usually associated with thymic abnormalities presented as thymic tumors (10%) or hyperplastic thymus (65%). The exact role of thymus in Myasthenia Gravis development is not clear, yet many patients benefit from thymectomy. The apoptotic ligand TNF-Related Apoptosis-Inducing Ligand is thought to be involved in the regulation of thymocyte counts, although conflicting results are reported. We investigated differential expression profiles of TNF-Related Apoptosis-Inducing Ligand and its transmembrane receptors, Nuclear Factor-kB activation status, and apoptotic cell counts in healthy thymic tissue and pathological thymus from Myasthenia Gravis patients. All tissues expressed TNF-Related Apoptosis-Inducing Ligand and its receptors, with hyperplastic tissue having the highest expression levels of death receptors DR4 and DR5. No detectable Nuclear Factor-kB activation, at least via the canonical Protein Kinase A-mediated p65 Ser276 phosphorylation, was evident in any of the tissues studied. Apoptotic cell counts were higher in MG-associated tissue compared to the normal thymus. Possible use of the TNF-Related Apoptosis-Inducing Ligand within the concept of an apoptotic ligand-mediated medical thymectomy in thymoma- or thymic hyperplasia-associated Myasthenia Gravis is also discussed.
重症肌无力是一种自身抗体介导的神经肌肉接头疾病，通常与胸腺异常有关，表现为胸腺瘤（约10%）或胸腺增生（约65%）。胸腺在重症肌无力发病中的具体作用尚不清楚，但许多患者可从胸腺切除术中获益。凋亡配体肿瘤坏死因子相关凋亡诱导配体被认为参与胸腺细胞数量的调节，尽管有相互矛盾的报道。我们研究了肿瘤坏死因子相关凋亡诱导配体及其跨膜受体的差异表达谱、核因子-κB激活状态以及重症肌无力患者健康胸腺组织和病理胸腺中的凋亡细胞计数。所有组织均表达肿瘤坏死因子相关凋亡诱导配体及其受体，增生组织中死亡受体DR4和DR5的表达水平最高。在所研究的任何组织中，均未检测到明显的核因子-κB激活，至少通过经典的蛋白激酶A介导的p65丝氨酸276磷酸化未检测到。与正常胸腺相比，重症肌无力相关组织中的凋亡细胞计数更高。还讨论了在胸腺瘤或胸腺增生相关的重症肌无力中，肿瘤坏死因子相关凋亡诱导配体在凋亡配体介导的医学胸腺切除概念中的可能应用。
