TY - JOUR
T1 - Ultrasensitive immunoassay allows measurement of serum neurofilament heavy in multiple sclerosis
AU - Verberk, Inge M.W.
AU - Koel-Simmelink, Marleen
AU - Twaalfhoven, Harry
AU - Vrenken, Hugo
AU - Korth, Carsten
AU - Killestein, Joep
AU - Teunissen, Charlotte E.
AU - Bridel, Claire
N1 - Funding Information: IV, MK, HT, CK, CB have nothing to disclose. HV has received research grants from Pfizer, MerckSerono, Novartis and Teva, speaker honoraria from Novartis, and consulting fees from MerckSerono; all funds were paid directly to his institution. JK has accepted speaker and consulting fees from Merck, Biogen, TEVA, Sanofi, Genzyme, Roche and Novartis. CT has a collaboration contract with ADx Neurosciences, performed contract research or received grants from Probiodrug, AC Immune, Biogen-Esai, CogRx, Toyama, Janssen prevention center, Boehringer, AxonNeurosciences, Fujirebio, EIP farma, PeopleBio and Roche. Funding Information: CB is supported by a Swiss MS Society Grant. Research of CT is supported by the European Commission ( Marie Curie International Training Network , JPND), Health Holland , the Dutch Research Council (ZonMW), The Weston Brain Institute and Alzheimer Netherland. Funders had no role in design of the study, collection, analysis and interpretation of data and in writing the manuscript. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - Background: Neurofilament heavy (NfH) is a promising biomarker for neuro-axonal damage in Multiple Sclerosis (MS). We compared the performance of high-sensitivity serum-NfH immunoassays, with as aim to investigate the value of serum-NfH as biomarker for MS. Methods: We measured serum-NfH in 76 MS patients with Simoa (one commercial, one in-house) or Luminex assays. Serum-NfH measured by the immunoassay with greatest sensitivity was related to clinical and radiological outcomes with age and sex-adjusted linear regression analysis, and to biological outcomes cerebrospinal fluid (CSF)-NfH, serum neurofilament light (NfL) and CSF-NfL with Spearman's correlation analysis. Results: With the commercial Simoa assay, we obtained 100% serum-NfH detectability (in-house Simoa: 70%, Luminex: 61%), with lowest coefficient of variation (CV) between duplicates of 11%CV (in-house Simoa: 22%CV, Luminex: 30%CV). Serum-NfH quantified with the commercial Simoa assay was associated with disease duration (standardized beta (sβ) = 0.28, p = 0.034), T2 lesion volume (sβ = 0.23, p = 0.041), and tended to associate with black hole count (sβ = 0.21, p = 0.084) but not with Expanded Disease Disability Score (EDSS) or normalized brain volume (all: p>0.10). Furthermore, serum-NfH showed correlations with CSF-NfH (rho = 0.27, p = 0.018) and serum-NfL (rho=0.44, p < 0.001), but not with CSF-NfL. Conclusions: Serum-NfH can be quantified with high-sensitivity technology. Cross-sectionally, we observed some weak correlations of serum-NfH with MS disease burden parameters, suggesting there might be some utility for serum-NfH as biomarker for MS disease burden.
AB - Background: Neurofilament heavy (NfH) is a promising biomarker for neuro-axonal damage in Multiple Sclerosis (MS). We compared the performance of high-sensitivity serum-NfH immunoassays, with as aim to investigate the value of serum-NfH as biomarker for MS. Methods: We measured serum-NfH in 76 MS patients with Simoa (one commercial, one in-house) or Luminex assays. Serum-NfH measured by the immunoassay with greatest sensitivity was related to clinical and radiological outcomes with age and sex-adjusted linear regression analysis, and to biological outcomes cerebrospinal fluid (CSF)-NfH, serum neurofilament light (NfL) and CSF-NfL with Spearman's correlation analysis. Results: With the commercial Simoa assay, we obtained 100% serum-NfH detectability (in-house Simoa: 70%, Luminex: 61%), with lowest coefficient of variation (CV) between duplicates of 11%CV (in-house Simoa: 22%CV, Luminex: 30%CV). Serum-NfH quantified with the commercial Simoa assay was associated with disease duration (standardized beta (sβ) = 0.28, p = 0.034), T2 lesion volume (sβ = 0.23, p = 0.041), and tended to associate with black hole count (sβ = 0.21, p = 0.084) but not with Expanded Disease Disability Score (EDSS) or normalized brain volume (all: p>0.10). Furthermore, serum-NfH showed correlations with CSF-NfH (rho = 0.27, p = 0.018) and serum-NfL (rho=0.44, p < 0.001), but not with CSF-NfL. Conclusions: Serum-NfH can be quantified with high-sensitivity technology. Cross-sectionally, we observed some weak correlations of serum-NfH with MS disease burden parameters, suggesting there might be some utility for serum-NfH as biomarker for MS disease burden.
KW - Blood biomarker
KW - Multiple sclerosis
KW - Neurofilament heavy
KW - Neurofilament light
KW - Simoa
UR - http://www.scopus.com/inward/record.url?scp=85101277210&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.msard.2021.102840
DO - https://doi.org/10.1016/j.msard.2021.102840
M3 - Article
C2 - 33626430
SN - 2211-0348
VL - 50
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
M1 - 102840
ER -