False positive plasma p-tau217 results associated with heterophilic antibody interference: A potential clinical pitfall.

INTRODUCTION

Plasma phosphorylated tau at threonine 217 (p-tau217) has emerged as one of the most promising blood-based biomarkers for Alzheimer's disease (AD). While rare, heterophilic antibodies (HAb) are a persistent potential confounding factor in immunoassays.

METHODS

Potential HAb interference in the Lumipulse G pTau217 assay in samples exhibiting concentrations > 10 pg/mL were investigated. Samples were subjected to HAb blocking reagent (HBT), and in some cases, polyethylene glycol (PEG) precipitation and serial dilutions.

RESULTS

In 14 of the 15 suspected HAb cases, HBT treatment greatly reduced measured p-tau217 concentrations. and in one of three specimens selected for further investigation, reduced Aβ42 concentrations PEG precipitation in the three selected samples also reduced p-tau217 concentrations, while serial dilution yielded mixed effects. Control specimens were unaffected by sample treatment or dilutions.

DISCUSSION: HAb may result in falsely elevated p-tau217 and p-tau217/Aβ42 ratio. HAb interference should be considered in cases of unusually high p-tau217 concentrations prior to clinical interpretation.

HIGHLIGHTS: Potential heterophile antibody (HAb) interference in the Lumipulse p-tau217 immunoassay was investigated. Investigation was performed using HAb blocking reagent, and in some cases also using PEG precipitation . Patients with p-tau217 concentrations > 10 pg/mL exhibited positive HAb interference in 14 of 15 cases. HAb interference can lead to falsely positive p-tau217/Aβ42 ratios.