Clinical Characterization and Outcome of Anti-IgLON5 Disease

Anti-IgLON5 disease is a neurological disorder associated with antibodies to IgLON5, a neuronal cell adhesion protein of unknown function. Most patients develop a combination of significant sleep disturbances (non-rapid eye movement (NREM) and rapid eye movement parasomnias with obstructive sleep apnoea), bulbar dysfunction (dysarthria, dysphagia, vocal cord paralysis or episodes of respiratory failure) and gait instability. Early autopsy studies showed deposits of phosphorylated tau protein mainly in neurons of the brainstem tegmentum, suggesting a primary neurodegenerative disease. However, the results of subsequent studies have provided increasing support for an immune-mediated pathogenesis. First, there is a strong association with the human leukocyte antigen (HLA) haplotype DRB1*10:01-DQB1*05 : 01, which is present in ~60% of patients (compared to 2% in the normal population); secondly, recent autopsy studies have shown the absence of abnormal tau deposits; and thirdly, in live neurons in culture, IgLON5 antibodies cause irreversible loss of surface IgLON5 clusters and cytoskeletal changes such as dystrophic neurites and axonal bulges. Together, these studies suggest that antibody-mediated disruption of IgLON5 function leads to neurofilament and cytoskeletal alterations that can potentially result in tau accumulation.

Over the last two years, an increase in diagnoses of anti-IgLON5 disease has been observed in the French Reference centre of Autoimmune Encephalitis. This could be related to a better knowledge of the disease, or to other yet unknown factors. Clinical characterisation of these patients is essential to understand the underlying reasons for the increase in diagnoses and to improve knowledge of this disease. Furthermore, the response of these patients to immunosuppressive drugs and the long-term prognosis remain unknown.