Serum Neurofilament Light and GFAP Are Associated With Disease Severity in Inflammatory Disorders With Aquaporin-4 or Myelin Oligodendrocyte Glycoprotein Antibodies

Abstract

Objective: To evaluate the potential of serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP) as disease biomarkers in neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibody (AQP4-ab) or myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD).Methods: Patients with AQP4-ab-positive NMOSD (n = 51), MOGAD (n = 42), and relapsing-remitting multiple sclerosis (RRMS) (n = 31 for sNfL and n = 22 for sGFAP testing), as well as healthy controls (HCs) (n = 28), were enrolled prospectively. We assessed sNfL and sGFAP levels using ultrasensitive single-molecule array assays. Correlations of sNfL and sGFAP levels with clinical parameters were further examined in AQP4-ab-positive NMOSD and MOGAD patients.Results: sNfL levels were significantly higher in patients with AQP4-ab-positive NMOSD (median 17.6 pg/mL), MOGAD (27.2 pg/mL), and RRMS (24.5 pg/mL) than in HCs (7.4 pg/mL, all p < 0.001). sGFAP levels were remarkably increased in patients with AQP4-ab-positive NMOSD (274.1 pg/mL) and MOGAD (136.7 pg/mL) than in HCs (61.4 pg/mL, both p < 0.001). Besides, sGFAP levels were also significantly higher in patients with AQP4-ab-positive NMOSD compared to those in RRMS patients (66.5 pg/mL, p < 0.001). The sGFAP/sNfL ratio exhibited good discrimination among the three disease groups. sNfL levels increased during relapse in patients with MOGAD (p = 0.049) and RRMS (p < 0.001), while sGFAP levels increased during relapse in all three of the disease groups (all p < 0.05). Both sNfL and sGFAP concentrations correlated positively with Expanded Disability Status Scale scores in AQP4-ab-positive NMOSD (β = 1.88, p = 0.018 and β = 2.04, p = 0.032) and MOGAD patients (β = 1.98, p = 0.013 and β = 1.52, p = 0.008).Conclusion: sNfL and sGFAP levels are associated with disease severity in AQP4-ab-positive NMOSD and MOGAD patients, and the sGFAP/sNfL ratio may reflect distinct disease pathogenesis.

Assessing attacks and treatment response rates among adult patients with NMOSD and MOGAD: Data from a nationwide registry in Argentina

“… 41 – 43 Additionally, sNfL levels increased during attacks in MOG-AD patients and both sNfL and sGFAP concentrations correlated positively with EDSS scores in NMOSD and MOG-AD patients. 42 …”

Serum neurofilament light chain in adult and pediatric patients with myelin oligodendrocyte glycoprotein antibody‐associated disease: Correlation with relapses and seizures

“…No randomization was performed to allocate subjects. This study was exploratory, no sample size calculation was performed, and the number of subjects used was determined based on previous studies of a similar nature (Chang et al, 2021;Mariotto et al, 2019).…”

“…In the last few years, several biomarkers for MOGAD, such as neurofilament light (NfL), have been investigated (Chang et al, 2021;Kim et al, 2020;Mariotto et al, 2017Mariotto et al, , 2019Mariotto et al, , 2021Schindler et al, 2021). NfL is a scaffolding protein of the neural cytoskeleton and is released into the cerebrospinal fluid (CSF) and blood following CNS axonal damage (Bacioglu et al, 2016;Khalil et al, 2018).…”

“…NfL is a scaffolding protein of the neural cytoskeleton and is released into the cerebrospinal fluid (CSF) and blood following CNS axonal damage (Bacioglu et al, 2016;Khalil et al, 2018). Previous studies reported that serum NfL (sNfL) levels were increased significantly in patients with MOGAD compared with healthy controls (HCs) that these increased levels were correlated with disease severity and that they might be predictive of the long-term outcome (Chang et al, 2021;Kim et al, 2020;Mariotto et al, 2019Mariotto et al, , 2021.…”

Longitudinal treatment responsiveness on plasma neurofilament light chain and glial fibrillary acidic protein levels in neuromyelitis optica spectrum disorder

“…Previous studies have reported no significant change in serum NfL levels between different treatment status in NMOSD patients. 9 , 24 However, these studies included only patients treated with corticosteroid or conventional oral immunosuppressants but not with newly emerging molecular targeted drugs. A recent Korean study reported that serum NfL levels in NMOSD patients treated with rituximab remained stable in the 2-year follow-up period.…”