Genetic Variation in Low-To-Medium-Affinity Fc? Receptors: Functional Consequences, Disease Associations, and Opportunities for Personalized Medicine.

ABSTRACT: Fc-gamma receptors (Fc?R) are the cellular receptors for Immunoglobulin G (IgG). Upon binding of complexed IgG, Fc?Rs can trigger various cellular immune effector functions, thereby linking the adaptive and innate immune systems. In humans, six classic Fc?Rs are known: one high-affinity receptor (Fc?RI) and five low-to-medium-affinity Fc?Rs (Fc?RIIA, -B and -C, Fc?RIIIA and -B). In this review we describe the five genes encoding the low-to-medium -affinity Fc?Rs (FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B), including well-characterized functionally relevant single nucleotide polymorphisms (SNPs), haplotypes as well as copy number variants (CNVs), which occur in distinct copy number regions across the locus. The evolution of the locus is also discussed. Importantly, we recommend a consistent nomenclature of genetic variants in the FCGR2/3 locus. Next, we focus on the relevance of genetic variation in the FCGR2/3 locus in auto-immune and auto-inflammatory diseases, highlighting pathophysiological insights that are informed by genetic association studies. Finally, we illustrate how specific Fc?R variants relate to variation in treatment responses and prognosis amongst autoimmune diseases, cancer and transplant immunology, suggesting novel opportunities for personalized medicine.

SUBMITTER: Nagelkerke SQ 

PROVIDER: S-EPMC6786274 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature