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Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder

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Item Type:Article
Title:Serum GFAP and NfL as disease severity and prognostic biomarkers in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder
Creators Name:Schindler, P., Grittner, U., Oechtering, J., Leppert, D., Siebert, N., Duchow, A.S., Oertel, F.C., Asseyer, S., Kuchling, J., Zimmermann, H.G., Brandt, A.U., Benkert, P., Reindl, M., Jarius, S., Paul, F., Bellmann-Strobl, J., Kuhle, J. and Ruprecht, K.
Abstract:BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a frequently disabling neuroinflammatory syndrome with a relapsing course. Blood-based disease severity and prognostic biomarkers for NMOSD are a yet unmet clinical need. Here, we evaluated serum glial fibrillary acidic protein (sGFAP) and neurofilament light (sNfL) as disease severity and prognostic biomarkers in patients with aquaporin-4 immunoglobulin (Ig)G positive (AQP4-IgG(+)) NMOSD. METHODS: sGFAP and sNfL were determined by single-molecule array technology in a prospective cohort of 33 AQP4-IgG(+) patients with NMOSD, 32 of which were in clinical remission at study baseline. Sixteen myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG(+)) patients and 38 healthy persons were included as controls. Attacks were recorded in all AQP4-IgG(+) patients over a median observation period of 4.25 years. RESULTS: In patients with AQP4-IgG(+) NMOSD, median sGFAP (109.2 pg/ml) was non-significantly higher than in MOG-IgG(+) patients (81.1 pg/ml; p = 0.83) and healthy controls (67.7 pg/ml; p = 0.07); sNfL did not substantially differ between groups. Yet, in AQP4-IgG(+), but not MOG-IgG(+) patients, higher sGFAP was associated with worse clinical disability scores, including the Expanded Disability Status Scale (EDSS, standardized effect size = 1.30, p = 0.007) and Multiple Sclerosis Functional Composite (MSFC, standardized effect size = - 1.28, p = 0.01). While in AQP4-IgG(+), but not MOG-IgG(+) patients, baseline sGFAP and sNfL were positively associated (standardized effect size = 2.24, p = 0.001), higher sNfL was only non-significantly associated with worse EDSS (standardized effect size = 1.09, p = 0.15) and MSFC (standardized effect size = - 1.75, p = 0.06) in patients with AQP4-IgG(+) NMOSD. Patients with AQP4-IgG(+) NMOSD with sGFAP > 90 pg/ml at baseline had a shorter time to a future attack than those with sGFAP ≤ 90 pg/ml (adjusted hazard ratio [95% confidence interval] = 11.6 [1.3-105.6], p = 0.03). In contrast, baseline sNfL levels above the 75th age adjusted percentile were not associated with a shorter time to a future attack in patients with AQP4-IgG(+) NMOSD. CONCLUSION: These findings suggest a potential role for sGFAP as biomarker for disease severity and future disease activity in patients with AQP4-IgG(+) NMOSD in phases of clinical remission.
Keywords:Neuromyelitis Optica Spectrum Disorder, Glial Fibrillary Acidic Protein, Neurofilament Light Chain Protein, Aquaporin-4 Immunoglobulin G, Myelin Oligodendrocyte Glycoprotein Immunoglobulin G, Biomarker, Serum
Source:Journal of Neuroinflammation
ISSN:1742-2094
Publisher:BioMed Central
Volume:18
Number:1
Page Range:105
Date:1 May 2021
Official Publication:https://doi.org/10.1186/s12974-021-02138-7
PubMed:View item in PubMed

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