Comparative analysis of three platforms for serum NfL quantification in healthy controls and MS patients

Neurofilament light chain (NfL) is a biomarker of neuroaxonal damage in various neurological conditions, including multiple sclerosis (MS). With new analytical platforms entering the market, standardization of serum NfL (sNfL) measurement is essential. This study compared sNfL levels across three assays - NF-light Advantage V2/Plus (Quanterix), Lumipulse G NfL blood (FujiRebio), and Elecsys NfL (Roche Diagnostics) - and derived conversion formulas for harmonization.

Serum samples from three cohorts including healthy donors (n=303) and MS patients (n=181) were analyzed across three platforms. Passing-Bablok regression and correlation analyses assessed inter-platform agreement and potential systematic differences. Assays were further evaluated for their ability to detect MS disease activity.

All platforms showed strong correlations (Pearson>0.98; Spearman>0.90, p<0.001). Absolute values from Elecsys were ∼6-fold lower than the other assays. Fourteen of 484 samples (2.90 %) showed substantial, retest-stable deviations (>4 SD) on at least one platform. After excluding outliers, conversion formulas were derived to transform the values to the NF-light Advantage V2/Plus scale: NfL=6.31 × [Elecsys NfL] + 2.33 ng/L; NfL=0.94 × [Lumipulse G NfL] + 1.30 ng/L. In MS patients, all platforms detected significant differences between relapse and remission (p<0.001). Age-adjusted Z scores from converted values yielded the highest effect sizes (Cohen's d: 0.84 for NF-light Advantage, 1.11 for Elecsys, 0.93 for Lumipulse).

The three platforms demonstrated high correlation and comparable performance in sNfL quantification. About 3 % of samples showed strong deviations, highlighting the need for vigilance and further harmonization. Age-adjusted Z scores may enhance clinical and research utility.