Functional consequences of allotypic polymorphisms in human immunoglobulin G subclasses

Heritable polymorphisms within the human IgG locus, collectively termed allotypes, have often been linked by statistical associations, but rarely mechanistically, to a wide range of disease states. One potential explanation for these associations is that IgG allotype alters host cell receptors' affinity for IgG, dampening or enhancing an immune response depending on the nature of the change and the receptors. In this work, a panel of allotypic antibody variants were evaluated using multiplexed, label-free biophysical methods and cell-based functional assays to determine what effect, if any, human IgG polymorphisms have on antibody function. While we observed several differences in Fc gamma R affinity among allotypes, there was little evidence of dramatically altered Fc gamma R-based effector function or antigen recognition activity associated with this aspect of genetic variability.

Automated summary

Heritable polymorphisms within the human IgG locus, collectively termed allotypes, have been statistically linked to various disease states. This study investigates the potential effects of IgG allotype on antibody function, specifically on Fc gamma R affinity and effector function. The results suggest that while there are differences in Fc gamma R affinity among allotypes, there is little evidence of significantly altered Fc gamma R-based effector function or antigen recognition activity associated with this genetic variability.