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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02237

Genetic variation in Low-to-medium-affinity Fcγ receptors: functional consequences, disease associations and opportunities for personalized medicine

 Sietse Q. Nagelkerke1*,  David E. Schmidt1, Masja de Haas2 and Taco W. Kuijpers1
  • 1AMC-Sanquin Landsteiner Laboratory, Netherlands
  • 2Sanquin Diagnostic Services, Netherlands

Fc-gamma receptors (FcγR) are the cellular receptors for Immunoglobulin G (IgG). and Upon binding of complexed IgG, FcγRs can trigger various cellular immune effector functions, thereby linking the adaptive and innate immune systems. In humans, six classic FcγRs are known: one high-affinity receptor (FcγRI) and five low-to-medium-affinity FcγRs (FcγRIIA, -B and -C, FcγRIIIA and -B). In this review we describe the five genes encoding the low-to-medium -affinity FcγRs (FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B), including functionally relevant single nucleotide polymorphisms (SNPs), haplotypes as well as copy number variants (CNVs), which occur in distinct copy number regions across the locus. 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 FcγR variants relate to variation in treatment responses and prognosis amongst autoimmune diseases, cancer and transplant immunology, suggesting novel opportunities for personalized medicine.

Keywords: Fc gamma receptor (FcγR), Genetic Variation, Autoinflammatory and autoimmunological diseases, Immunotherapy, mechanisms of disease

Received: 19 Jul 2019; Accepted: 04 Sep 2019.

Copyright: © 2019 Nagelkerke, Schmidt, de Haas and Kuijpers. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Sietse Q. Nagelkerke, AMC-Sanquin Landsteiner Laboratory, Amsterdam, 1066, Netherlands, s.nagelkerke@sanquin.nl