Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Immunol Cell Biol. 2024 Nov;102(10):891-906. doi: 10.1111/imcb.12825. Epub 2024 Oct 13.
Myasthenia gravis (MG) is the most frequent immune-mediated neurological disorder, characterized by fluctuating muscle weakness. Specific recognition of self-antigens by T-cell receptors (TCRs) and B-cell receptors (BCRs), coupled with T-B cell interactions, activates B cells to produce autoantibodies, which are critical for the initiation and perpetuation of MG. The immune repertoire comprises all functionally diverse T and B cells at a specific time point in an individual, reflecting the essence of immune selectivity. By sequencing the nucleotide sequences of TCRs and BCRs, it is possible to track individual T- and B-cell clones. This review delves into the generation of autoreactive TCRs and BCRs in MG and comprehensively examines the applications of immune repertoire sequencing in understanding disease pathogenesis, developing diagnostic and prognostic markers and informing targeted therapies. We also discuss the current limitations and future potential of this approach.
重症肌无力(MG)是最常见的免疫介导的神经疾病,其特征是肌肉无力波动。T 细胞受体(TCRs)和 B 细胞受体(BCRs)对自身抗原的特异性识别,加上 T-B 细胞相互作用,激活 B 细胞产生自身抗体,这对于 MG 的启动和持续至关重要。免疫库包含个体在特定时间点的所有功能多样化的 T 和 B 细胞,反映了免疫选择性的本质。通过对 TCR 和 BCR 的核苷酸序列进行测序,可以跟踪个体 T 和 B 细胞克隆。这篇综述深入探讨了 MG 中自身反应性 TCR 和 BCR 的产生,并全面研究了免疫库测序在了解疾病发病机制、开发诊断和预后标志物以及指导靶向治疗方面的应用。我们还讨论了这种方法的当前局限性和未来潜力。