Mind the Gap: How Interspecies Variability in IgG and Its Receptors May Complicate Comparisons of Human and Non-human Primate Effector Function

Conclusions The sheer number of factors to consider when translating observations between macaques and humans makes the process a challenging, multidimensional one. Differences in the structures and activities of IgG subclasses, and polymorphisms in protein sequence and post-translational modification of antibody receptors are a subset of the many relevant considerations. Copy number variation, splice variants, and alleles with sequence variation outside of coding regions have been associated with a diversity of phenotypes in humans (183, 213–217), and are presumed to exist in NHP. A number of differences in the patterns of cellular expression of FcγRs between species are well-established, and while genetically-associated differences in expression levels likely exist, they have not been fully characterized. Linkage disequilibrium between FcRs and a diversity of major and minor alleles make it difficult to define the potential effect of these polymorphisms with high confidence even in large cohorts. Thus, the process of precisely translating results between species is a complex and potentially intractable challenge. However, the highly significant contributions to drug development demonstrates that macaques can nonetheless serve as an excellent preclinical model. When considering exceptional scenarios, several simplifying assumptions may help to smooth the process. The first—treating the members of the macaque genus largely interchangeably—has...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research