Development and multi-center validation of a fully automated digital immunoassay for neurofilament light chain: toward a clinical blood test for neuronal injury

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • David Wilson - , Quanterix Corp (Autor:in)
  • Dandan Chan - , Quanterix Corp (Autor:in)
  • Lei Chang - , Quanterix Corp (Autor:in)
  • Robert Mathis - , Quanterix Corp (Autor:in)
  • Inge Verberk - , Amsterdam University Medical Centers (UMC) (Autor:in)
  • Xavier Montalban - , Vall d'Hebron Research Institute (VHIR) (Autor:in)
  • Manuel Comabella - , Vall d'Hebron Research Institute (VHIR) (Autor:in)
  • Nicolas Fissolo - , Vall d'Hebron Research Institute (VHIR) (Autor:in)
  • Bibi Bielekova - , National Institutes of Health (NIH) (Autor:in)
  • Ruturaj Masvekar - , National Institutes of Health (NIH) (Autor:in)
  • Tanuja Chitnis - , Harvard Medical School (HMS) (Autor:in)
  • Tjalf Ziemssen - , Klinik und Poliklinik für Neurologie (Autor:in)
  • Katja Akgün - , Klinik und Poliklinik für Neurologie (Autor:in)
  • Kaj Blennow - , University of Gothenburg (Autor:in)
  • Henrik Zetterberg - , University of Gothenburg (Autor:in)
  • Wolfgang Brück - , Universitätsmedizin Göttingen (Autor:in)
  • Gavin Giovannoni - , Barts Health NHS Trust (Autor:in)
  • Sharmilee Gnanapavan - , Barts Health NHS Trust (Autor:in)
  • Stefan Bittner - , Universitätsmedizin Mainz (Autor:in)
  • Frauke Zipp - , Universitätsmedizin Mainz (Autor:in)
  • Giancarlo Comi - , Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele (Autor:in)
  • Roberto Furlan - , Vita-Salute San Raffaele University (Autor:in)
  • Sylvain Lehmann - , CHU Montpellier (Autor:in)
  • Simon Thebault - , Ottawa Hospital Research Institute (Autor:in)
  • Mark Freedman - , Ottawa Hospital Research Institute (Autor:in)
  • Amit Bar-Or - , University of Pennsylvania (Autor:in)
  • Marty Kramer - , Sanofi-Aventis (Autor:in)
  • Markus Otto - , Universitätsklinikum Ulm (Autor:in)
  • Steffen Halbgebauer - , Universitätsklinikum Ulm (Autor:in)
  • Kevin Hrusovsky - , Quanterix Corp (Autor:in)
  • Tatiana Plavina - , Quanterix Corp (Autor:in)
  • Michael Khalil - , Medizinische Universität Graz (Autor:in)
  • Fredrik Piehl - , Karolinska Institutet (Autor:in)
  • Heinz Wiendl - , Westfälische Wilhelms-Universität Münster (Autor:in)
  • Ludwig Kappos - , Universität Basel (Autor:in)
  • Aleksandra Maceski - , Universität Basel (Autor:in)
  • Eline Willemse - , Universität Basel (Autor:in)
  • David Leppert - , Universität Basel (Autor:in)
  • Charlotte Teunissen - , Amsterdam University Medical Centers (UMC) (Autor:in)
  • Jens Kuhle - , Universität Basel (Autor:in)

Abstract

Neurofilament light chain (NfL) has emerged as a promising biomarker for detecting and monitoring axonal injury. Until recently, NfL could only be reliably measured in cerebrospinal fluid, but digital single molecule array (Simoa) technology has enabled its precise measurement in blood samples where it is typically 50 100 times less abundant. We report development and multi-center validation of a novel fully automated digital immunoassay for NfL in serum for informing axonal injury status. Methods: A 45-min immunoassay for serum NfL was developed for use on an automated digital analyzer based on Simoa technology. The analytical performance (sensitivity, precision, reproducibility, linearity, sample type) was characterized and then cross validated across 17 laboratories in 10 countries. Analytical performance for clinical NfLmeasurement was examined in individual patients with relapsing remitting multiple sclerosis (RRMS) after 3 months of disease modifying treatment (DMT) with fingolimod. Results: The assay exhibited a lower limit of detection (LLoD) of 0.05 ng/L, a lower limit of quantification (LLoQ) of 0.8 ng/L, and between-laboratory imprecision <10 % across 17 validation sites. All tested samples had measurable NfL concentrations well above the LLoQ. In matched pre post treatment samples, decreases in NfL were observed in 26/29 RRMS patients three months afterDMT start, with significant decreases detected in a majority of patients. Conclusions: The sensitivity characteristics and reproducible performance across laboratories combined with full automation make this assay suitable for clinical use for NfL assessment, monitoring in individual patients, and crosscomparisons of results across multiple sites.

Details

OriginalspracheEnglisch
Seiten (von - bis)322-331
Seitenumfang10
FachzeitschriftClinical chemistry and laboratory medicine
Jahrgang62
Ausgabenummer2
Frühes Online-Datum13 Sept. 2023
PublikationsstatusVeröffentlicht - 26 Jan. 2024
Peer-Review-StatusJa

Externe IDs

Scopus 85172480921

Schlagworte

Schlagwörter

  • Biomarkers, Hematologic Tests, Humans, Immunoassay, Intermediate Filaments, Neurofilament Proteins, Neurons, Reproducibility of Results