Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD.

Watanabe M; Nakamura Y; Michalak Z; Isobe N; Barro C; Leppert D; Matsushita T; Hayashi F; Yamasaki R; Kuhle J; Kira JI

doi:10.1212/WNL.0000000000008160

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Journal article

Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD.

Watanabe M From the Departments of Neurology (M.W., Y.N., T.M., F.H., R.Y., J.-i.K.) and Neurological Therapeutics (N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Neurology (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland.
Nakamura Y From the Departments of Neurology (M.W., Y.N., T.M., F.H., R.Y., J.-i.K.) and Neurological Therapeutics (N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Neurology (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland.
Michalak Z From the Departments of Neurology (M.W., Y.N., T.M., F.H., R.Y., J.-i.K.) and Neurological Therapeutics (N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Neurology (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland.
Isobe N From the Departments of Neurology (M.W., Y.N., T.M., F.H., R.Y., J.-i.K.) and Neurological Therapeutics (N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Neurology (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland.
Barro C From the Departments of Neurology (M.W., Y.N., T.M., F.H., R.Y., J.-i.K.) and Neurological Therapeutics (N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Neurology (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland.
Leppert D From the Departments of Neurology (M.W., Y.N., T.M., F.H., R.Y., J.-i.K.) and Neurological Therapeutics (N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Neurology (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland.
Matsushita T From the Departments of Neurology (M.W., Y.N., T.M., F.H., R.Y., J.-i.K.) and Neurological Therapeutics (N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Neurology (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland.
Hayashi F From the Departments of Neurology (M.W., Y.N., T.M., F.H., R.Y., J.-i.K.) and Neurological Therapeutics (N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Neurology (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland.
Yamasaki R From the Departments of Neurology (M.W., Y.N., T.M., F.H., R.Y., J.-i.K.) and Neurological Therapeutics (N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Neurology (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland.
Kuhle J From the Departments of Neurology (M.W., Y.N., T.M., F.H., R.Y., J.-i.K.) and Neurological Therapeutics (N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Neurology (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland.
Kira JI From the Departments of Neurology (M.W., Y.N., T.M., F.H., R.Y., J.-i.K.) and Neurological Therapeutics (N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and Neurology (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland. kira@neuro.med.kyushu-u.ac.jp jens.kuhle@usb.ch.

2019-09-01

Published in:

Neurology. - 2019

Glial Fibrillary Acidic Protein

English 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.

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