Department of Immunology, NSW Health Pathology-ICPMR, Westmead Hospital, Sydney, NSW 2145, Australia.
Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia.
Int J Mol Sci. 2024 Jul 21;25(14):7956. doi: 10.3390/ijms25147956.
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 () 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)-DRB110:01 and HLA-DQB105:01 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.
抗 IgLON5（IgLON5-IgG）相关疾病是一种新定义的临床实体。本文献综述旨在评估其发病机制，这仍然是一个关键问题。支持原发性神经退行性疾病机制的特征包括非炎症性 tau 病理特征和微管相关蛋白 tau () H1/H1 基因型的过度表达，如在其他散发性 tau 病中所见。相比之下，IgLON5 的细胞表面定位、抗 IgLON5 抗体在体外发挥直接致病性的能力以及破坏 IgLON5 与其结合伴侣 HLA-DRB110:01 和 HLA-DQB105:01 等位基因的相互作用的能力，与 IgLON5 肽的高亲和力结合，以及对免疫疗法的反应性，都支持原发性自身免疫过程。抗 IgLON5 相关疾病的表现和病程是异质的；因此，我们假设在该疾病队列中可能同时存在多种免疫机制。
