Serum biomarkers in myelin oligodendrocyte glycoprotein antibody-associated disease

Abstract

Objective: To test the hypothesis that the pattern of serum biomarkers of disease activity and disability in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) will be different from those in neuromyelitis optica spectrum disorder (NMOSD) with anti-aquaporin-4 antibodies (AQP4-Abs).

Methods: Using ultrasensitive single-molecule array assays, we measured neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and tau in the sera of consecutive patients with MOGAD (n = 16) and NMOSD with AQP4-Ab (n = 33). Serum biomarker levels were compared between patients in relapse and remission states, and correlations between the levels of these biomarkers and Expanded Disability Status Scale (EDSS) scores were analyzed within each group.

Results: In the MOGAD group, the serum tau level was higher in a relapse state than in a remission state (relapse vs remission: 0.5 [0.4-0.5] vs 0.2 [0.1-0.3] pg/mL, p = 0.027). Both serum levels of NfL and tau correlated with the EDSS score (NfL: r = 0.684, p = 0.003; tau: r = 0.524, p = 0.045). Meanwhile, in the NMOSD group, serum NfL and GFAP levels were higher in a relapse state than in a remission state (relapse vs remission: NfL, 34.8 [12.2-62.3] vs 13.0 [11.3-20.0] pg/mL, p = 0.010; GFAP, 253.8 [150.6-303.0] vs 104.4 [93.9-127.9] pg/mL, p = 0.016). Only the serum GFAP level correlated with the EDSS score (r = 0.485, p = 0.012).

Conclusion: The pattern of serum biomarkers of disease activity and disability in MOGAD showed a distinct feature from those in NMOSD with AQP4-Ab, which implicates different pathogeneses between the 2 diseases.

Figure 1. Comparison of serum biomarkers in patients with MOGAD and NMOSD with AQP4-Ab

(A and B) Serum NfL levels, (C and D) serum GFAP levels, and (E and F) serum tau levels were compared between patients with MOGAD and NMOSD with AQP4-Abs. In panels A, C, and E, all samples from each group were included. In panels B, D, and F, each group was subdivided into relapse and remission states. The line in the center represents the median. The whiskers indicate the interquartile range. The p values were obtained via analysis of covariance, adjusted for age and Expanded Disability Status Scale score. *p < 0.05. AQP4-Abs = anti-aquaporin-4 antibodies; GFAP = glial fibrillary acidic protein; MOGAD = myelin oligodendrocyte glycoprotein antibody–associated disease; NfL = neurofilament light chain; NMOSD = neuromyelitis optica spectrum disorder.

Figure 2. Correlation of serum biomarkers with age and EDSS score

Correlation between age and serum levels of (A) NfL, (B) GFAP, and (C) tau in patients with MOGAD or NMOSD with anti–aquaporin-4 antibodies (AQP4-Abs). Correlation of the serum level with (D) NfL, (E) GFAP, and (F) tau with the EDSS score in patients with MOGAD or NMOSD with AQP4-Abs. The dotted lines indicate 95% CIs. EDSS = Expanded Disability Status Scale; GFAP = glial fibrillary acidic protein; MOGAD = myelin oligodendrocyte glycoprotein antibody–associated disease; NfL = neurofilament light chain; NMOSD = neuromyelitis optica spectrum disorder.