Anti-IgLON5 disease: a novel topic beyond neuroimmunology

Zhang, Yi-Zong Heng; Ni, You; Gao, Yining; Shen, Dingding; He, Lu; Yin, Dou; Meng, Huanyu; Zhou, Qinming; Hu, Ji; Chen, Sheng

doi:10.4103/1673-5374.355742

Cited by 12 publications

(10 citation statements)

References 71 publications

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“…(1) It has been firstly observed that anti-IgLON5 antibodies can cause relatively long-lasting effects, with motor impairment persisting for 3 months in passive transfer animal models. (2) The motor impairment associated with anti-IgLON5 antibodies may be related to the nigrostriatal dopaminergic pathway. (3) The deposition of p-Tau has been observed in vivo for the first time, indicating long-term exposure to anti-IgLON5 antibodies can lead to neurodegenerative changes.…”

Section: Discussionmentioning

confidence: 99%

Purified Serum IgG from a Patient with Anti-IgLON5 Antibody Cause Long-Term Movement Disorders with Impaired Dopaminergic Pathways in Mice

Gao,

Li,

Luo

et al. 2023

Biomedicines

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Background: Anti-IgLON5 disease is a rare autoimmune disease of the central nervous system. It typically manifests as a chronic condition, characterized by cognitive impairments, movement disorders, and sleep disorders. The mechanisms underlying movement disorders in this disease remain poorly understood due to a lack of research. Furthermore, this disease exhibits both neuroimmune and neurodegenerative characteristics. The objective of this study is to explore the underlying mechanisms of movement disorders caused by anti-IgLON5 antibodies for the first time. Methods: Antibodies were purified from the serum of a confirmed patient of anti-IgLON5 disease. The passive transfer animal models were employed, where antibodies were continuously injected into the substantia nigra pars compacta (SNc) of the mouse midbrain using stereotactic injection to explore the mechanism of movement disorder. The effects of anti-IgLON5 antibodies on dopaminergic neurons in the SNc and neurodegeneration were examined through immunohistochemistry. Changes in neurotransmitter levels in the basal ganglia were assessed using high-performance liquid chromatography. Additionally, RNA-seq was employed to identify the differentially expressed genes associated with the short-term and long-term effects of anti-IgLON5 antibody on the SNc. Results: Mice injected with anti-IgLON5 antibodies in the SNc exhibited persistent movement impairments for up to 3 months. One week after antibody injection, the number of TH neurons significantly decreased compared to the control group, accompanied by reduced projection fibers in the basal ganglia and decreased dopamine levels. After 3 months of antibody injection, an increase in phosphorylated Tau was observed in the SNc of the midbrain. Additionally, long-term sustained activation of microglia was detected in the SNc. The differentially expressed genes of long-term effects of IgLON5 antibodies were different from their short-term effects on the SNc. Conclusion: Purified serum IgG from a patient with anti-IgLON5 antibodies can cause long-term movement disorder in mice. The movement disorders appear to be linked to the impaired dopaminergic pathway, and the increased p-Tau showed neurodegenerative changes induced by the anti-IgLON5 antibody.

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Section: Discussionmentioning

confidence: 99%

Purified Serum IgG from a Patient with Anti-IgLON5 Antibody Cause Long-Term Movement Disorders with Impaired Dopaminergic Pathways in Mice

Gao,

Li,

Luo

et al. 2023

Biomedicines

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“…No specific cutoff values have been established as positivity of these Abs is not expected in the general population. The relatively low titers detected in our patient may be explained by the early stage of the disease as an Abs titer is expected to increase as the disease progresses ( 28 , 29 ). There are also significant associations between certain haplotypes and anti-IgLON5 disease, indicating a specific genetic susceptibility to the disease.…”

Section: Discussionmentioning

confidence: 79%

IgLON5 autoimmunity in a patient with Creutzfeldt–Jakob disease: case report and review of literature

Li,

Chen,

Zhang

et al. 2024

Front. Neurol.

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ObjectiveWe present the case of a patient with clinical and imaging features of sporadic Creutzfeldt–Jakob disease (sCJD) and positive IgLON5 antibodies (Abs) in the serum and CSF.Case reportA 66-year-old Chinese man presented to the hospital with a stroke-like episode, followed by rapidly progressive cognitive decline, mutism, and parkinsonism. The MRI results showed a cortical ribboning sign in diffusion-weighted MRI, periodic triphasic waves with a slow background in EEG, and positive protein 14–3-3 in CSF. There were matching IgLON5 Abs in the serum and CSF. A literature review showed positive autoimmune encephalitis Abs or autoimmune inflammatory disease between 0.5 and 8.6% among patients with clinical suspicion of CJD, most commonly anti-voltage-gated potassium channel (VGKC) complex and anti-N-methyl-D-aspartate receptor (NMDAR) Abs; however, IgLON5 autoimmunity in CJD has been rarely reported. This is an intriguing association as both conditions have been associated with brain deposits of phosphorylated tau protein.ConclusionIgLON5 Abs may be observed in patients with a diagnosis of CJD; it is unknown whether a synergistic effect of IgLON5 Abs with CJD exists, increasing neurodegenerative changes.

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“…Anti-IgLON5 encephalitis is a rare neurological entity that combines autoimmunization with neurodegeneration, which has heterogenous manifestations such as sleep disorder, gait abnormality, bulbar symptoms, as well as cognitive impairment, with or without chorea [ 2 , 3 ]. Most commonly, this disease is diagnosed among elderly patients with no sex predominance [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Coexistence of anti-NMDAR and anti-IgLON5 antibodies in an autoimmune encephalitis patient: The first case report

Tian,

Han,

Lenahan

et al. 2024

Heliyon

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Anti-IgLON5 disease: a novel topic beyond neuroimmunology

Cited by 12 publications

References 71 publications

Purified Serum IgG from a Patient with Anti-IgLON5 Antibody Cause Long-Term Movement Disorders with Impaired Dopaminergic Pathways in Mice

Purified Serum IgG from a Patient with Anti-IgLON5 Antibody Cause Long-Term Movement Disorders with Impaired Dopaminergic Pathways in Mice

IgLON5 autoimmunity in a patient with Creutzfeldt–Jakob disease: case report and review of literature

Coexistence of anti-NMDAR and anti-IgLON5 antibodies in an autoimmune encephalitis patient: The first case report

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