Allergen-antibody complexes activate human neutrophils via FcγR-independent phagocytosis in lab study

This laboratory study investigated how complexes of allergen and specific IgG antibodies (AICs) activate human neutrophils. Researchers isolated neutrophils from birch pollen allergic and non-allergic donors, primed them with cytokines (GM-CSF and IFN-γ), and then pulsed them with either non-complexed allergen, standard AICs, or effector-attenuated LALA-AICs. The study assessed FcγR expression, phagocytosis of fluorescence-labelled allergen, DNA-release (NET-release), and allergen-presenting activity for autologous T-cells.

Cytokine priming upregulated FcγRI/CD64 and downregulated FcγRIII/CD16 on neutrophils, while FcγRII/CD32 remained unaltered. Neutrophils phagocytosed the larger AIC and LALA-AIC complexes more effectively than smaller complexes or non-complexed allergen. Notably, while standard AICs induced NET-release, the attenuated LALA-AICs did not. The allergen-presenting activity results were mixed: T-cell proliferation was inconclusive when neutrophils were pulsed with standard AICs but was enhanced with LALA-AICs compared to non-complexed allergen.

Safety and tolerability data were not reported for this in vitro model. Key limitations include the study's purely mechanistic, laboratory-based design, the lack of reported sample size or statistical analyses, and inconclusive results regarding T-cell proliferation with standard AICs. The findings suggest a potential FcγR-independent pathway for allergen phagocytosis and presentation by neutrophils, with FcγR-mediated NET induction possibly interfering with T-cell activation. However, the direct clinical relevance for treating allergic disease remains unestablished.