Hend Abd El Baky, Nadav I Weinstock, Gull Zareen Khan Sial, Mark D Hicar
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We initially performed a literature review to summarize the Ab characteristics of autoantibodies related to some of the more common disorders, including N-methyl-d-aspartate receptor (NMDAR) and leucine-rich, glioma-inactivated 1 (LGI-1). Next, we performed data analysis from selected studies that sequenced Ig genes to further characterize NMDAR and LGI-1 autoantibodies including CDR3 length distribution, variable gene sequence usage, and isotype use. We found that CDR3 length of NMDAR autoantibodies was normally distributed whereas the CDR3 length distribution of LGI-1 autoantibodies was skewed, suggesting that there is no global structural restriction on types of autoantibodies that can cause encephalitis. We also found that IgG1-IgG3 were the main NMDAR autoantibody isotypes detected, while IgG4 was the major isotype used in autoantibodies from LGI-1 encephalitis. 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引用次数: 0
摘要
自身免疫性小儿神经系统疾病的表型和表现各不相同,因此诊断具有挑战性。其病理机制也各不相同,包括细胞介导和抗体介导的自身免疫、副肿瘤综合征和感染后过程。近年来,一些研究描述了这些疾病所涉及的自身抗体的特征。其中一些研究使用了一组有限的可变基因片段。我们试图比较与一些较常见疾病相关的自身抗体的 Ab 特性,以发现特定的 Ab 标志是否普遍与神经自身免疫性疾病相关。我们首先进行了文献综述,总结了与一些较常见疾病相关的自身抗体的抗体特征,包括N-甲基-d-天冬氨酸受体(NMDAR)和富亮氨酸胶质瘤灭活1(LGI-1)。接下来,我们对部分对 Ig 基因进行测序的研究进行了数据分析,以进一步确定 NMDAR 和 LGI-1 自身抗体的特征,包括 CDR3 长度分布、可变基因序列使用和同种型使用。我们发现,NMDAR自身抗体的CDR3长度呈正态分布,而LGI-1自身抗体的CDR3长度分布则呈倾斜状,这表明可导致脑炎的自身抗体类型在结构上并无总体限制。我们还发现,IgG1-IgG3 是检测到的主要 NMDAR 自身抗体同工型,而 IgG4 是 LGI-1 脑炎自身抗体的主要同工型。这些发现有助于我们了解自身免疫性脑炎,并有助于今后更好地诊断和治疗这些疾病。
Comparison of B Cell Variable Region Gene Segment Characteristics in Neuro-autoantibodies.
Autoimmune pediatric neurologic diseases have variable phenotypes and presentations, making diagnosis challenging. The pathologic mechanisms are also distinct, including cell-mediated and Ab-mediated autoimmunity, paraneoplastic syndromes, and postinfectious processes. In recent years a number of studies have described the characteristics of the autoantibodies involved in a number of these diseases. Some of the described Abs use a restricted set of variable gene segments. We sought to compare the Ab characteristics of autoantibodies related to some of the more common disorders to discover whether specific Ab signatures are universally associated with neuroautoimmune diseases. We initially performed a literature review to summarize the Ab characteristics of autoantibodies related to some of the more common disorders, including N-methyl-d-aspartate receptor (NMDAR) and leucine-rich, glioma-inactivated 1 (LGI-1). Next, we performed data analysis from selected studies that sequenced Ig genes to further characterize NMDAR and LGI-1 autoantibodies including CDR3 length distribution, variable gene sequence usage, and isotype use. We found that CDR3 length of NMDAR autoantibodies was normally distributed whereas the CDR3 length distribution of LGI-1 autoantibodies was skewed, suggesting that there is no global structural restriction on types of autoantibodies that can cause encephalitis. We also found that IgG1-IgG3 were the main NMDAR autoantibody isotypes detected, while IgG4 was the major isotype used in autoantibodies from LGI-1 encephalitis. These findings are useful for our understanding of autoimmune encephalitis and will help facilitate better diagnosis and treatment of these conditions in the future.