Myasthenia gravis (MG) is an acquired autoimmune disorder caused by autoantibodies binding acetylcholine receptors (AChR), muscle-specific kinase (MuSK), agrin or low-density lipoprotein receptor-related protein 4 (Lrp4). These autoantibodies inhibit neuromuscular transmission by blocking the function of these proteins, and thereby cause fluctuating skeletal muscle weakness. Several reports suggest that these autoantibodies might also affect the central nervous system (CNS) in MG patients. A comprehensive overview of the timing and localization of the expression of MG-related antigens in other organs is currently lacking. To investigate the spatio-temporal expression of MG-related genes outside skeletal muscle, we used in silico tools to assess public expression databases. Acetylcholine esterase, nicotinic AChR α1 subunit, agrin, collagen Q, Dok7, Lrp4, MuSK and rapsyn were included as MG-related genes because of their well-known involvement in either congenital or autoimmune MG. We investigated expression of MG-related genes in 1) all human tissues using GTEx data, 2) specific brain regions, 3) neurodevelopmental stages, and 4) cell types using datasets from the Allen Institute for Brain Sciences. MG-related genes show heterogenous spatio-temporal expression patterns in the human body as well as in the CNS. For each of these genes several (new) tissues, brain areas and cortical cell types with (relatively) high expression were identified suggesting a potential role for these genes outside skeletal muscle. The possible presence of MG-related antigens outside skeletal muscle suggests that autoimmune MG, congenital MG or treatments targeting the same proteins may affect MG-related protein function in other organs.

中文翻译：

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重症肌无力相关基因表达的时间和定位

重症肌无力（MG）是由结合乙酰胆碱受体（AChR），肌肉特异性激酶（MuSK），凝集素或低密度脂蛋白受体相关蛋白4（Lrp4）的自身抗体引起的获得性自身免疫疾病。这些自身抗体通过阻断这些蛋白质的功能来抑制神经肌肉的传递，从而引起骨骼肌无力的波动。一些报告表明，这些自身抗体也可能影响MG患者的中枢神经系统（CNS）。当前缺乏对MG相关抗原在其他器官中表达的时间和定位的全面概述。为了调查骨骼肌外MG相关基因的时空表达，我们使用计算机软件评估了公共表达数据库。乙酰胆碱酯酶，烟碱型AChRα1亚基，凝集素，胶原蛋白Q，Dok7，由于Lrp4，MuSK和rapsyn与先天性或自身免疫性MG有关，因此它们被列为MG相关基因。我们调查了1）使用GTEx数据在所有人类组织中，2）特定大脑区域，3）神经发育阶段和4）使用来自艾伦脑科学研究所的数据集的细胞类型中MG相关基因的表达。MG相关基因在人体和中枢神经系统中均表现出异质的时空表达模式。对于这些基因中的每一个，鉴定了具有（相对）高表达的几种（新）组织，脑区域和皮质细胞类型，表明这些基因在骨骼肌之外具有潜在作用。骨骼肌以外可能存在MG相关抗原，这表明自身免疫性MG，