Association of IgG1 Antibody Clearance with FcγRIIA Polymorphism and Platelet Count in Infliximab-Treated Patients

The Fc gamma RIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R polymorphism (histidine > arginine at position 131) influences affinity for multimeric IgG2. Platelet Fc gamma RIIA has been reported to contribute to IgG-containing immune-complexe clearance. Given our finding that platelet Fc gamma RIIA actually binds monomeric IgG, we investigated the role of platelets and Fc gamma RIIA in IgG antibody elimination. We used pharmacokinetics analysis of infliximab (IgG1) in individuals with controlled Crohn's disease. The influence of platelet count and Fc gamma RIIA polymorphism was quantified by multivariate linear modelling. The infliximab half-life increased with R allele number (13.2, 14.4 and 15.6 days for HH, HR and RR patients, respectively). It decreased with increasing platelet count in R carriers: from approximate to 20 days (RR) and approximate to 17 days (HR) at 150 x 10(9) /L, respectively, to approximate to 13 days (both HR and RR) at 350 x 10(9) /L. Moreover, a flow cytometry assay showed that infliximab and monomeric IgG1 bound efficiently to platelet Fc gamma RIIA H and R allotypes, whereas panitumumab and IgG2 bound poorly to the latter. We propose that infliximab (and presumably any IgG1 antibody) elimination is partly due to an unappreciated mechanism dependent on binding to platelet Fc gamma RIIA, which is probably tuned by its affinity for IgG2.

Automated summary

Fc gamma RIIA/CD32A is expressed on platelets and some endothelial cells, playing a role in binding IgG antibodies, which may contribute to their elimination. Platelet Fc gamma RIIA's affinity for different IgG subclasses influences the clearance of antibodies like infliximab.