Longitudinal follow-up of serum biomarkers in patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Recently, several serum biomarkers have been proposed in Neuromyelitis Optica Spectrum Disorders (NMOSD) to monitor disease activity. OBJECTIVE: The objective of the study is to evaluate the longitudinal clinical value of serum biomarkers in patients with NMOSD. METHODS: We prospectively recruited consecutive NMOSD patients with anti-aquaporin-4 antibody and obtained serum samples at enrollment, after 6-12 months of follow-up (main period), and at attacks. Using single-molecule array assays, we evaluated longitudinal changes of serum neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and GFAP/NfL levels. RESULTS: Overall, 64 patients (58 women) were enrolled (age: 51 years, disease duration: 6.7 years) and 133 samples were obtained. Among patients who did not develop new attacks during the main period (n = 62), serum levels of NfL, GFAP, and GFAP/NfL were significantly decreased over time in patients with attacks (<2 months) at enrollment (n = 14 (23%)), whereas serum NfL and GFAP levels gradually increased in the others (n = 48 (77%)). During the study, five (8%) patients developed new attacks; only serum GFAP levels increased consistently upon these events compared with baseline levels. To differentiate attacks from remissions, serum GFAP levels showed the largest area under the receiver operating characteristic curve (0.876, 95% confidence interval: 0.801-0.951). CONCLUSION: Among NfL, GFAP, and GFAP/NfL, serum GFAP might be the most appropriate for monitoring NMOSD longitudinally, which warrants future confirming studies.

Serum biomarkers in myelin oligodendrocyte glycoprotein antibody-associated disease.

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.