Biomarkers of Neuronal and Glial Injury in Leucine-Rich Glioma Inactivated-1 (LGI1) Autoimmune Encephalitis Patients: A Pilot Study
Tyler Borko1, Christopher Mizenko1, Ryan Kammeyer1, Alanna Ritchie1, Sean Selva1, Britney Barrera1, Brooke Valdez1, Stefan Sillau1, Gregory Owens1, Timothy Vollmer1, Kavita Nair1, Jeffrey Bennett1, Amanda Piquet1
1Department of Neurology, University of Colorado Anschutz School of Medicine
Objective:
To examine concentrations of plasma-based biomarkers obtained from leucine-rich glioma inactivated 1 (LGI1) autoimmune encephalitis (AIE) patients and compare to healthy controls (HC).
Background:
Markers of neuronal and glial injury and have been adapted for monitoring disease activity and severity in individuals with various neurodegenerative and neuroinflammatory disorders. Currently, there is a lack of biomarkers that inform on disease activity, prognosis, and treatment in LGI1-AIE.
Design/Methods:
Neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and chemokine ligand 13 (CXCL-13) levels in LGI1-AIE and HC participants will be compared in plasma samples using Quanterix SR-XTM SIMOA. Plasma concentration of NFL, GFAP and CXCL-13 will be longitudinally evaluated and correlated with clinical outcome measures using mixed model regression.
Results:
Twelve LGI1-AIE patients, seven of whom have longitudinal collections, have samples collected to date. Preliminary results for 4 longitudinal plasma samples from LGI1-AIE patients (mean age 70.9, 50% female) were analyzed with initial collection at diagnosis showing a mean NfL (17.0 pg/mL), GFAP (110.5 pg/mL), and CXCL-13 (106.9 pg/mL). Comparing samples longitudinally over 18-24 months showed an overall decrease over time with mean NfL (8.7 pg/mL), GFAP (115.9 pg/mL) and CXCL-13 (41.7 pg/mL). This was compared to our 33 HC cohort (mean age 46.3, 69% female), mean NfL (6.8 pg/mL), GFAP (68.2 pg/mL, and CXCL-13 (65.4 pg/mL). Biomarker analysis on additional LGI1-AIE patients is ongoing including exploratory evaluation of synaptosomal-associated protein 25 (SNAP25) on CSF samples.
Conclusions:
Preliminary results show NfL, GFAP, and CXCL-13 levels are higher in LGI1-AIE at the time of their disease onset versus HCs. All biomarkers in LGI1-AIE patients showed a trend of decreasing concentrations over time, with the most robust reduction seen in CXCL-13 levels.