Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood

Clin Chem Lab Med. 2023 Jan 31;61(7):1245-1254. doi: 10.1515/cclm-2022-1181. Print 2023 Jun 27.

Abstract

Objectives: Neurofilament light chain (NfL) concentration in blood is a biomarker of neuro-axonal injury in the nervous system and there now exist several assays with high enough sensitivity to measure NfL in serum and plasma. There is a need for harmonization with the goal of creating a certified reference material (CRM) for NfL and an early step in such an effort is to determine the best matrix for the CRM. This is done in a commutability study and here the results of the first one for NfL in blood is presented.

Methods: Forty paired individual serum and plasma samples were analyzed for NfL on four different analytical platforms. Neat and differently spiked serum and plasma were evaluated for their suitability as a CRM using the difference in bias approach.

Results: The correlation between the different platforms with regards to measured NfL concentrations were very high (Spearman's ρ≥0.96). Samples spiked with cerebrospinal fluid (CSF) showed higher commutability compared to samples spiked with recombinant human NfL protein and serum seems to be a better choice than plasma as the matrix for a CRM.

Conclusions: The results from this first commutability study on NfL in serum/plasma showed that it is feasible to create a CRM for NfL in blood and that spiking should be done using CSF rather than with recombinant human NfL protein.

Keywords: certified reference material; commutability; harmonization; neurofilament light.

MeSH terms

  • Biomarkers
  • Humans
  • Intermediate Filaments*
  • Neurofilament Proteins*
  • Plasma
  • Recombinant Proteins
  • Reference Standards
  • Serum

Substances

  • Neurofilament Proteins
  • Biomarkers
  • Recombinant Proteins