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New knowledge on anti-IgLON5 disease.

Carles Gaig¹, Lidia Sabater²

¹Service of Neurology, Hospital Clinic de Barcelona.

Current Opinion in Neurology

|April 2, 2024

Summary

Anti-IgLON5 disease presents with sleep and neurological issues, featuring a novel tauopathy. Autoimmune factors and neurofilament light chain levels are key for diagnosis and predicting immunotherapy response.

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Area of Science:

Neurology
Immunology
Pathology

Background:

Anti-Immunoglobulin Like Domain Containing 5 (IgLON5) disease is a rare autoimmune disorder characterized by unique sleep disturbances and diverse neurological symptoms.
Initial findings revealed a novel tauopathy in the brainstem tegmentum, suggesting a neurodegenerative component.
Recent advancements have shed light on diagnostic markers, immunotherapy response predictors, and the autoimmune pathogenesis.

Purpose of the Study:

To review recent findings in Anti-IgLON5 disease, focusing on clinical presentation, diagnostic biomarkers, and underlying pathogenesis.
To highlight the association of IgLON5 antibodies with specific neurological syndromes.
To discuss the role of neurofilament light chain as a prognostic biomarker and the implications of new neuropathological and in vitro studies.

Main Methods:

Review of recent literature on Anti-IgLON5 disease.
Analysis of clinical case reports and diagnostic criteria.
Examination of neuropathological findings and in vitro experimental data.

Main Results:

Patients with Anti-IgLON5 disease may present with symptoms mimicking neurodegenerative dementia, progressive supranuclear palsy (PSP), or motor-neuron disease (MND).
Low serum and cerebrospinal fluid neurofilament light chain levels at disease onset may predict response to immunotherapy.
Neuropathological studies suggest tau deposits may be a late-stage event, potentially secondary to IgLON5 antibody effects.

Conclusions:

Anti-IgLON5 disease should be considered in atypical presentations of MND, neurodegenerative dementia, and PSP.
Neurofilament light chain levels show promise as a biomarker for disease prognosis.
Neuropathological and experimental evidence strengthens the autoimmune hypothesis for Anti-IgLON5 disease.