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

Abstract

<b>Objective:</b> 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). <b>Methods:</b> Patients with AQP4-ab-positive NMOSD (<i>n</i> = 51), MOGAD (<i>n</i> = 42), and relapsing-remitting multiple sclerosis (RRMS) (<i>n</i> = 31 for sNfL and <i>n</i> = 22 for sGFAP testing), as well as healthy controls (HCs) (<i>n</i> = 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. <b>Results:</b> 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 <i>p</i> < 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 <i>p</i> < 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, <i>p</i> < 0.001). The sGFAP/sNfL ratio exhibited good discrimination among the three disease groups. sNfL levels increased during relapse in patients with MOGAD (<i>p</i> = 0.049) and RRMS (<i>p</i> < 0.001), while sGFAP levels increased during relapse in all three of the disease groups (all <i>p</i> < 0.05). Both sNfL and sGFAP concentrations correlated positively with Expanded Disability Status Scale scores in AQP4-ab-positive NMOSD (β = 1.88, <i>p</i> = 0.018 and β = 2.04, <i>p</i> = 0.032) and MOGAD patients (β = 1.98, <i>p</i> = 0.013 and β = 1.52, <i>p</i> = 0.008). <b>Conclusion:</b> 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.