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Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic

The fragment crystallizable (Fc) domain of antibodies is responsible for their protective function and long-lasting serum half-life via Fc-mediated effector function, transcytosis, and recycling through its interaction with Fc receptors (FcRs) expressed on various immune leukocytes, epithelial, and...

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Autores principales: Kim, Jin, Lee, Ji Young, Kim, Han Gil, Kwak, Min Woo, Kang, Tae Hyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431278/
https://www.ncbi.nlm.nih.gov/pubmed/34502398
http://dx.doi.org/10.3390/ijms22179489
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author Kim, Jin
Lee, Ji Young
Kim, Han Gil
Kwak, Min Woo
Kang, Tae Hyun
author_facet Kim, Jin
Lee, Ji Young
Kim, Han Gil
Kwak, Min Woo
Kang, Tae Hyun
author_sort Kim, Jin
collection PubMed
description The fragment crystallizable (Fc) domain of antibodies is responsible for their protective function and long-lasting serum half-life via Fc-mediated effector function, transcytosis, and recycling through its interaction with Fc receptors (FcRs) expressed on various immune leukocytes, epithelial, and endothelial cells. Therefore, the Fc–FcRs interaction is a control point of both endogenous and therapeutic antibody function. There are a number of reported genetic variants of FcRs, which include polymorphisms in (i) extracellular domain of FcRs, which change their affinities to Fc domain of antibodies; (ii) both cytoplasmic and intracellular domain, which alters the extent of signal transduction; and (iii) the promoter region of the FcRs gene, which affects the expression level of FcRs, thus being associated with the pathogenesis of disease indications. In this review, we firstly describe the correlation between the genetic variants of FcRs and immunological disorders by individual differences in the extent of FcRs-mediated regulations. Secondly, we discuss the influence of the genetic variants of FcRs on the susceptibility to infectious diseases or cancer in the perspective of FcRs-induced effector functions. Overall, we concluded that the genetic variants of FcRs are one of the key elements in the design of antibody therapeutics due to their variety of clinical outcomes among individuals.
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spelling pubmed-84312782021-09-11 Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic Kim, Jin Lee, Ji Young Kim, Han Gil Kwak, Min Woo Kang, Tae Hyun Int J Mol Sci Review The fragment crystallizable (Fc) domain of antibodies is responsible for their protective function and long-lasting serum half-life via Fc-mediated effector function, transcytosis, and recycling through its interaction with Fc receptors (FcRs) expressed on various immune leukocytes, epithelial, and endothelial cells. Therefore, the Fc–FcRs interaction is a control point of both endogenous and therapeutic antibody function. There are a number of reported genetic variants of FcRs, which include polymorphisms in (i) extracellular domain of FcRs, which change their affinities to Fc domain of antibodies; (ii) both cytoplasmic and intracellular domain, which alters the extent of signal transduction; and (iii) the promoter region of the FcRs gene, which affects the expression level of FcRs, thus being associated with the pathogenesis of disease indications. In this review, we firstly describe the correlation between the genetic variants of FcRs and immunological disorders by individual differences in the extent of FcRs-mediated regulations. Secondly, we discuss the influence of the genetic variants of FcRs on the susceptibility to infectious diseases or cancer in the perspective of FcRs-induced effector functions. Overall, we concluded that the genetic variants of FcRs are one of the key elements in the design of antibody therapeutics due to their variety of clinical outcomes among individuals. MDPI 2021-08-31 /pmc/articles/PMC8431278/ /pubmed/34502398 http://dx.doi.org/10.3390/ijms22179489 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kim, Jin
Lee, Ji Young
Kim, Han Gil
Kwak, Min Woo
Kang, Tae Hyun
Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic
title Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic
title_full Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic
title_fullStr Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic
title_full_unstemmed Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic
title_short Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic
title_sort fc receptor variants and disease: a crucial factor to consider in the antibody therapeutics in clinic
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431278/
https://www.ncbi.nlm.nih.gov/pubmed/34502398
http://dx.doi.org/10.3390/ijms22179489
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