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

Xuechun Chang,Yuxin Li,Chuanzhen Lu,Jiahong Lu,Min Wang,Chongbo Zhao,Jian Yu,Jingzi Zhangbao,Chao Quan,Liang Wang,Wenjuan Huang,Haiqing Li,Lei Zhou

doi:10.3389/fimmu.2021.647618

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.

Highlights

Neuromyelitis optica spectrum disorder (NMOSD) comprises a spectrum of inflammatory autoimmune disorders of the central nervous system (CNS) with a predilection for the optic nerves and spinal cord [1]
Results: serum neurofilament light (sNfL) levels were significantly higher in patients with aquaporin-4 antibody (AQP4-ab)-positive NMOSD, MOG-ab-associated disease (MOGAD) (27.2 pg/mL), and relapsing-remitting multiple sclerosis (RRMS) (24.5 pg/mL) than in healthy controls (HCs) (7.4 pg/mL, all p < 0.001). serum glial fibrillary acidic protein (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)
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

Summary

Introduction

Neuromyelitis optica spectrum disorder (NMOSD) comprises a spectrum of inflammatory autoimmune disorders of the central nervous system (CNS) with a predilection for the optic nerves and spinal cord [1]. The majority of NMOSD patients have antibodies to aquaporin-4 (AQP4) water channels, which are situated predominantly on the end-feet of astrocytic processes [2, 3]. AQP4-antibody-positive NMOSD (AQP4ab+NMOSD) is considered to be an autoimmune astrocytopathy with secondary demyelination. Using cell-based assays, myelin oligodendrocyte glycoprotein antibodies (MOG-ab) have been detected in a subset of NMOSD patients that are AQP4-ab negative [4, 5]. Neuropathologic findings of cases with MOG-ab show predominant demyelination yet preservation of astrocytes, distinct from the astrocytopathy observed in AQP4-ab+NMOSD [6, 7]. MOG-ab-associated disease (MOGAD) has recently been proposed as a distinct disease entity independent of NMOSD [8, 9]

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Results

Conclusion