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.

Keywords: aquaporin-4; glial fibrillary acidic protein; myelin oligodendrocyte glycoprotein; neurofilament light; neuromyelitis optica spectrum disorder.

Figure 1

Comparisons of sGFAP and sNfL levels among the different groups. (A,B) Correlations of sNfL and sGFAP levels with age in HCs. (C,E) sNfL and sGFAP levels were compared among all the samples from patients with AQP4-antibody-positive NMOSD, MOGAD, and RRMS, as well as from HCs. (D,F) Samples from the three disease groups were divided into relapse and remission stages and were compared. Boxes depict the median and interquartile range (IQR), with the median represented by the line in the center, and whiskers extending from minimum to maximum values. The dotted lines represent the 90th percentiles of sNfL or sGFAP concentrations in HCs. sNfL, serum neurofilament light; sGFAP, serum glial fibrillary acidic protein; HC, healthy control; AQP4, aquaporin 4; NMOSD, neuromyelitis optica spectrum disorders; MOGAD, myelin oligodendrocyte glycoprotein-antibody-associated diseases; RRMS, relapsing-remitting multiple sclerosis. The p-values were obtained with a mixed-effect model adjusted for age and EDSS scores (*p < 0.05, **p < 0.01, and ***p < 0.001). In the figure, AQP4 stands for AQP4-antibody-positive NMOSD; MOG stands for MOGAD.

Figure 2

sGFAP/sNfL ratios among the different groups. The sGFAP/sNfL ratios were compared among all the samples from patients with AQP4-antibody-positive NMOSD, MOGAD, and RRMS, as well as from HCs. Boxes depict the median and interquartile range (IQR), with the median represented by the line in the center, and whiskers extending from minimum to maximum values. sNfL, serum neurofilament light; sGFAP, serum glial fibrillary acidic protein; HC, healthy control; AQP4, aquaporin 4; NMOSD, neuromyelitis optica spectrum disorders; MOGAD, myelin oligodendrocyte glycoprotein-antibody-associated diseases; RRMS, relapsing-remitting multiple sclerosis. **p < 0.01, and ***p < 0.001. In the figure, AQP4 stands for AQP4-antibody-positive NMOSD; MOG stands for MOGAD.