Anti-IgLON5 encephalitis is associated with anti-retinal immunological reactivity without retinal alteration

Anti-IgLON5 disease is a recently defined autoimmune disorder of the central nervous system associated with autoantibodies against IgLON5. This progressive condition, combining features of autoimmunity and neurodegeneration, presents with highly heterogeneous symptoms, including sleep disorders, bulbar symptoms, oculomotor dysfunction, gait disturbances, and subsequent cognitive decline. Recent reports have also described cases of papillitis. The target antigen, IgLON5, is a cell adhesion protein whose role is not fully understood. In humans, it is mainly expressed in the brain and testis. IgLON5 transcripts are also expressed in the retina. However, retinal involvement is not classically explored in these patients. In this cross-sectional observational study, we investigated whether anti-IgLON5 antibodies might target retinal structures, and correlated these findings with ophthalmological assessments. Six patients were diagnosed with anti-IgLON5 antibody encephalitis at Toulouse University Hospital. Identification of the anti-IgLON5 antibody was performed by immunofluorescence on transfected cells using serum and CSF. Anti-retinal antibodies were detected by an indirect immunofluorescence method on sections of monkey retina. Patients underwent a systematic ophthalmological examination including an anatomical and electrophysiological assessment. Anti-retinal antibody identification revealed specific staining of the inner plexiform layer in all patients, which was not observed in control individuals. However, morphological and electrophysiological ophthalmological examinations did not reveal any common features between the patients. Although retinal involvement is rarely reported, these findings suggest a possible role for the retina in the pathophysiology of anti-IgLON5 encephalitis. They support the relevance of considering ophthalmological monitoring in patients with IgLON5-related disease.