Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune mediated astrocytopathies. Glial fibrillary acidic protein (GFAP) and S100B, two astrocyte specific, and neurofilament light chain (NfL), a neuron specific biomarker are reported to be elevated in CSF and serum or plasma in acute phases of NMOSD. Serum NfL is a predictor of relapse activity in multiple sclerosis (MS). However, whether serum levels of NfL (sNfL), GFAP (sGFAP) or S100B (sS100B) levels can be prognostic biomarkers for future acute disease activity in NMOSD has not been elucidated.
To test the prognostic potential of sGFAP, sS100B and sNfL levels during remission phase as biomarker for future relapses in NMOSD with aquaporin-4-IgG.
Median values of sGFAP, sS100B and sNfL were calculated from 47 serum samples from 18 patients in remission (>180 days after last relapse), followed for up to 10 years, and marked cut-off levels for “high” and “low” sGFAP (141.6 pg/mL), sS100B (8.6 pg/mL), and sNfL (33.9 pg/mL), respectively. Kaplan-Meier analysis, univariable and a multivariable (adjusted for age, sex, time from recent relapse and treatment) Cox-hazard model were used to compare the time to and hazard risk of the next relapse between the high and low groups for all three markers.
Twenty-five first post-relapse/remission phase samples from these 18 patients (11 had one relapse, 7 had two relapses) were selected for analyses. Patients in the high sGFAP group experienced future relapses earlier than those with low sGFAP levels (median 3710 versus 922 days, p = 0.0047) and had higher risk of future relapses (unadjusted hazard ratio (HR): 5.6 [95% CI 1.5–21.0], p = 0.010; adjusted hazard ratio: 9.5 [95% CI 1.9–47.0], p = 0.0061). In contrast, high sS100B and sNfL levels were unable to identify patients at increased risk for relapses.
We illustrate the prognostic capacity of an astrocyte specific marker, sGFAP, for future relapses in stable NMOSD. This further supports the value of this blood biomarker for potential future clinical application in guiding and monitoring treatment response of patients with NMOSD. The failure of sNfL as a neuronal marker in this capacity for NMOSD may reflect the pathogenetic differences between this disease and MS. The failure of sS100B may result from its pharmacokinetic profile as a short-lived marker in acute NMOSD, but not in stable disease.