Evaluation of Plasma Neurofilament Light Chain Levels as a Biomarker of Neuronal Injury in the Active and Chronic Phases of Autoimmune Neurologic Disorders

Ryan Kammeyer; Christopher Mizenko; Stefan Sillau; Alanna Richie; Gregory Owens; Kavita V Nair; Enrique Alvarez; Timothy L Vollmer; Jeffrey L Bennett; Amanda L Piquet

doi:10.3389/fneur.2022.689975

Evaluation of Plasma Neurofilament Light Chain Levels as a Biomarker of Neuronal Injury in the Active and Chronic Phases of Autoimmune Neurologic Disorders

Front Neurol. 2022 Mar 2:13:689975. doi: 10.3389/fneur.2022.689975. eCollection 2022.

Authors

Affiliations

¹ Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
² Department of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
³ Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Abstract

Objective: To evaluate plasma neurofilament light (NfL) levels in autoimmune neurologic disorders (AINDs) and autoimmune encephalitis (AE).

Background: Each particular neural autoantibody syndrome has a different clinical phenotype, making one unifying clinical outcome measure difficult to assess. While this is a heterogeneous group of disorders, the final common pathway is likely CNS damage and inflammation. Defining a biomarker of CNS injury that is easily obtainable through a blood sample and reflects a positive treatment response would be highly advantageous in future therapeutic trials. Measurement of blood concentration of neurofilament light (NfL) chain, however, may provide a biomarker of central nervous system (CNS) injury in AE and other AINDs. Here we provide an initial evaluation of plasma NfL levels in AE as well as other AINDs during active and chronic phases of disease and demonstrate its potential utility as a minimally-invasive biomarker for AE and AINDs.

Design/methods: Patients were retrospectively identified who were enrolled in the biorepository at the Rocky Mountain MS Center at the University of Colorado, or were prospectively enrolled after initial presentation. Patients had a well-defined AIND and were followed between 2014 and 2021. NfL was tested using the Single Molecule Array (SIMOA) technology. Patients with headaches but without other significant neurologic disease were included as controls.

Results: Twenty-six plasma and 14 CSF samples of patients with AINDs, and 20 plasma control samples stored in the biorepository were evaluated. A positive correlation was found between plasma and CSF NfL levels for patients with an AIND (R ² = 0.83, p < 0.001). Elevated plasma levels of NfL were seen in patients with active AE compared to controls [geometric mean (GM) 51.4 vs. 6.4 pg/ml, p = 0.002]. Patients with chronic symptoms (>6 months since new or worsening symptoms) of AE or cerebellar ataxia (CA) showed a trend toward lower plasma NfL levels (GM 15.1 pg/ml) compared to active AE or CA. Six patients with longitudinal, prospective sampling available demonstrated a trend in decreased plasma NfL levels over time.

Conclusions: Our findings support the use of plasma NfL as a potential minimally-invasive biomarker of CNS injury.

Keywords: autoimmune encephalitis (AE); autoimmune neurological disorders; biomarker; cerebellar ataxia; neurofilament (NF); neurofilament light (NfL) chain.