To assess NfL and GFAP as biomarkers of disease severity and mortality in anti-IgLON5 disease.

Anti-IgLON5 disease presents with diverse symptoms, with variable severity and impact on patient’s outcomes.

Patients diagnosed with anti-IgLON5 disease at a national reference center for autoimmune encephalitis (2016-2024) and available sera and/or CSF were included. Anti-IgLON5 disease composite score (ICS) was retrospectively evaluated at diagnosis, last visit, and other timepoints when samples were collected. NfL and GFAP concentrations were measured by Simoa. Correlations between NfL, GFAP, and ICS were assessed using Spearman’s rank correlation. A Cox regression model adjusted for age was used to assess the impact of NfL and GFAP on 2-year mortality risk.

Thirty patients were included (60% male; median age at diagnosis 72 years, median ICS at diagnosis 18, IQR 13-24; 35 sera, 22 CSF). Only serum NfL (sNfL, median 25 pg/mL) was significantly correlated with total ICS (R=0.38, p=0.025). Both sNfL and serum GFAP (sGFAP, median 141 pg/mL) were significantly correlated with the bulbar score (R=0.39, p=0.020 and R=0.34, p=0.044). In 26 patients sampled <4 months after diagnosis (median ICS at last visit 14, IQR 10-21; median survival 69 months), neither sNfL nor sGFAP were significantly correlated with total or partial ICS at last visit (median 19 months after diagnosis); sNfL was age-independently associated with 2-year mortality (HR 1.06, 95% CI 1.01-1.11; p=0.010). In 4 patients with longitudinal sera, sNfL kinetics mirrored ICS evolution over time. CSF NfL (median 1,409 pg/mL) and GFAP (median 7,904 pg/mL) were not significantly correlated with ICS, nor associated with mortality.

sNfL is a biomarker of anti-IgLON5 disease severity, particularly bulbar symptoms. While sNfL at diagnosis may help predict mortality, it does not seem to predict the extent of disease severity in the long-term. sNfL longitudinal measurement might aid in monitoring patients’ evolution and treatment response.