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Impact of Human FcγR Gene Polymorphisms on IgG-Triggered Cytokine Release: Critical Importance of Cell Assay Format.

Front Immunol. 2019-01; 
HussainKhiyam, HargreavesChantal E, RowleyTania F, SoppJoshua M, LathamKate V, BhattaPallavi, SheringtonJohn, CutlerRona M, HumphreysDavid P, GlennieMartin J, StreffordJonathan C, CraggMa
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… nM for FcγRI, FcγRIIb and FcγRIV in PBS 0.075% Tween-80 (VWR, M126–100mL), pH 7.4. For the His-tagged FcγRIII, biotinylated anti-His IgG1 (GenScript, A00613) was spotted in duplicate and 3-fold dilution onto the sensor and 100 nM his-FcγRIII (equally diluted in …

摘要

Monoclonal antibody (mAb) immunotherapy has transformed the treatment of allergy, autoimmunity, and cancer. The interaction of mAb with Fc gamma receptors (FcγR) is often critical for efficacy. The genes encoding the low-affinity FcγR have single nucleotide polymorphisms (SNPs) and copy number variation that can impact IgG Fc:FcγR interactions. Leukocyte-based assays remain one of the industry standards for determining mAb efficacy and predicting adverse responses in patients. Here we addressed the impact of FcγR genetics on immune cell responses in these assays and investigated the importance of assay format. FcγR genotyping of 271 healthy donors was performed using a Multiplex Ligation-Dependent Pro... More

关键词

Fc gamma receptor polymorphism,Fc gamma receptors,antibody immunotherapy,cytokine release assays,cytokine release synd