Antibody Fc: Chapter 12. Fcγ Receptor Polymorphisms and Susceptibility to Infection

Antibody Fc: Chapter 12. Fcγ Receptor Polymorphisms and Susceptibility to Infection
ISBN-10
0128060336
ISBN-13
9780128060339
Series
Antibody Fc
Category
Medical
Pages
358
Language
English
Published
2013-08-06
Publisher
Elsevier Inc. Chapters
Author
Menna R. Clatworthy

Description

Fcγ receptors (FcγR) mediate many effector functions of antibody and are critical for defense against pathogens, including bacteria, viruses, and parasites. A number of single nucleotide polymorphisms have been identified in both activating and inhibitory FcγR genes that affect either the binding affinity for IgG or receptor function. Reviewing the available evidence from murine knockout mice, in vitro studies utilizing human cells, and genetic studies in humans, the current view on the role of FcγR polymorphisms in susceptibility to infection will be summarized here. Genetic studies have often yielded conflicting results, which may be due to small sample size or the inherent difficulties associated with genotyping the FCGR locus, or they may reflect differences in the functional importance of interactions between FcγR and its ligands (IgG versus CRP) in differing clinical manifestations of infectious disease. The engagement of the inhibitory FcγR limits the proinflammatory response initiated by FcγR ligation. FCGR polymorphisms that favor activating FcγR may result in excessive inflammation that is deleterious to the host, despite its efficacy in eliminating the pathogen. Overall, pathogen encounter is likely to be the main factor driving the retention of FCGR polymorphisms within the gene pool. Evidence suggests that potent infections, such as malaria, have exerted a significant evolutionary pressure on the maintenance and prevalence of FcγR polymorphisms in different populations.

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