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Abstract
Objective To test the hypothesis that serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), which are an intermediate astrocyte and neuron filaments, respectively, are clinically useful biomarkers of disease activity and disability in neuromyelitis optica spectrum disorders (NMOSD).
Methods Levels of GFAP and NfL in serum (sGFAP and sNfL, respectively) and in CSF samples were measured in healthy controls (HCs) (n = 49; 49 serum samples), patients with NMOSD (n = 33; 42 CSF and 102 serum samples), and patients with multiple sclerosis (MS) (n = 49; 53 CSF and 91 serum samples) by ultrasensitive single-molecule array assays. Association of sGFAP and sNfL levels with clinical parameters was determined.
Results For both GFAP and NfL, CSF and serum levels were strongly correlated. Both were higher in the serum of patients with NMOSD than in HCs (both p < 0.001). Moreover, sGFAP was higher in NMOSD than in MS (median 207.7 vs 121.1 pg/mL, p < 0.001). In NMOSD, sGFAP concentration increased after recent relapse (540.9 vs 152.9 pg/mL, p < 0.001). Multivariate analyses indicated that sGFAP and sNfL were associated with Expanded Disability Status Scale score in NMOSD (p = 0.026 and p < 0.001, respectively). Higher sGFAP/sNfL quotient at relapse differentiated NMOSD from MS with a sensitivity of 73.0% and a specificity of 75.8%.
Conclusions sGFAP and sNfL are likely to be good biomarkers of disease activity and disability, and the sGFAP/sNfL quotient at relapse is a potential diagnostic marker for NMOSD.
Glossary
- AQP4=
- aquaporin-4;
- CI=
- confidence interval;
- DMD=
- disease-modifying drug;
- EDSS=
- Expanded Disability Status Scale;
- GFAP=
- glial fibrillary acidic protein;
- HCs=
- healthy controls;
- IgG=
- immunoglobulin G;
- IQR=
- interquartile range;
- MS=
- multiple sclerosis;
- Nf=
- neurofilament;
- NfL=
- neurofilament light chain;
- NMOSD=
- neuromyelitis optica spectrum disorders;
- PPMS=
- primary progressive multiple sclerosis;
- ROC=
- receiver operating characteristic;
- RRMS=
- relapsing-remitting multiple sclerosis;
- sGFAP=
- serum glial fibrillary acidic protein;
- sNfL=
- serum neurofilament light chain;
- SPMS=
- secondary progressive multiple sclerosis
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
- Received December 8, 2018.
- Accepted in final form May 2, 2019.
- © 2019 American Academy of Neurology
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