First Infusion Reactions are Mediated by FcγRIIIb and Neutrophils.

ABSTRACT:

Purpose

Administration of therapeutic monoclonal antibodies (mAbs) is frequently accompanied by severe first infusion reactions (FIR). The mechanism driving FIR is still unclear. This study aimed to investigate the cellular and molecular mechanisms causing FIR in humanized mouse models and their potential for evaluating FIR risk in patients.

Methods

Mice humanized for Fc gamma receptors (FcγRs) were generated by recombination-mediated genomic replacement. Body temperature, cytokine release and reactive oxygen species (ROS) were measured to assess FIR to mAbs.

Results

Infusion of human mAb specific for mouse transferrin receptor (HamTfR) into FcγR-humanized mice, produced marked transient hypothermia accompanied by an increase in inflammatory cytokines KC and MIP-2, an

SUBMITTER: Weber F 

PROVIDER: S-EPMC6021477 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature