PDF(Pubmed)
Abstract：
Anti-IgLON5 (IgLON5-IgG)-associated disease is a newly defined clinical entity. This literature review aims to evaluate its pathogenesis, which remains a pivotal question. Features that favour a primary neurodegenerative mechanism include the non-inflammatory tauopathy neuropathological signature and overrepresentation of microtubule-associated protein tau (MAPT) H1/H1 genotype as seen in other sporadic tauopathies. In contrast, the cell-surface localisation of IgLON5, capability of anti-IgLON5 antibodies to exert direct in vitro pathogenicity and disrupt IgLON5 interactions with its binding partners, human leukocyte antigen (HLA)-DRB1*10:01 and HLA-DQB1*05:01 allele preponderance with high affinity binding of IgLON5 peptides, and responsiveness to immunotherapy favour a primary autoimmune process. The presentation and course of anti-IgLON5-associated disease is heterogenous; hence, we hypothesise that a multitude of immune mechanisms are likely simultaneously operational in this disease cohort.
摘要：
抗IgLON5（IgLON5-IgG）相关疾病是一种新定义的临床实体。这篇文献综述旨在评估其发病机制，这仍然是一个关键问题。有利于原发性神经退行性机制的特征包括非炎性tau病神经病理特征和微管相关蛋白tau（MAPT）H1/H1基因型的过度表达，如其他散发性tau病中所见。相比之下,IgLON5的细胞表面定位，抗IgLON5抗体发挥直接体外致病性并破坏IgLON5与其结合伴侣相互作用的能力，人类白细胞抗原（HLA）-DRB1*10:01和HLA-DQB1*05:01等位基因优势与IgLON5肽的高亲和力结合，对免疫疗法的反应性有利于原发性自身免疫过程。抗IgLON5相关疾病的表现和病程是异质性的；因此，我们假设在该疾病队列中多种免疫机制可能同时起作用.
