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Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies

The presence of fucose on IgG1 Asn-297 N-linked glycan is the modification of the human IgG1 Fc structure with the most significant impact on FcɣRIII affinity. It also significantly enhances the efficacy of antibody dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells in vitro, induce...

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Autores principales: Golay, Josée, Andrea, Alain E., Cattaneo, Irene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279668/
https://www.ncbi.nlm.nih.gov/pubmed/35844552
http://dx.doi.org/10.3389/fimmu.2022.929895
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author Golay, Josée
Andrea, Alain E.
Cattaneo, Irene
author_facet Golay, Josée
Andrea, Alain E.
Cattaneo, Irene
author_sort Golay, Josée
collection PubMed
description The presence of fucose on IgG1 Asn-297 N-linked glycan is the modification of the human IgG1 Fc structure with the most significant impact on FcɣRIII affinity. It also significantly enhances the efficacy of antibody dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells in vitro, induced by IgG1 therapeutic monoclonal antibodies (mAbs). The effect of afucosylation on ADCC or antibody dependent phagocytosis (ADCP) mediated by macrophages or polymorphonuclear neutrophils (PMN) is less clear. Evidence for enhanced efficacy of afucosylated therapeutic mAbs in vivo has also been reported. This has led to the development of several therapeutic antibodies with low Fc core fucose to treat cancer and inflammatory diseases, seven of which have already been approved for clinical use. More recently, the regulation of IgG Fc core fucosylation has been shown to take place naturally during the B-cell immune response: A decrease in α-1,6 fucose has been observed in polyclonal, antigen-specific IgG1 antibodies which are generated during alloimmunization of pregnant women by fetal erythrocyte or platelet antigens and following infection by some enveloped viruses and parasites. Low IgG1 Fc core fucose on antigen-specific polyclonal IgG1 has been linked to disease severity in several cases, such as SARS-CoV 2 and Dengue virus infection and during alloimmunization, highlighting the in vivo significance of this phenomenon. This review aims to summarize the current knowledge about human IgG1 Fc core fucosylation and its regulation and function in vivo, in the context of both therapeutic antibodies and the natural immune response. The parallels in these two areas are informative about the mechanisms and in vivo effects of Fc core fucosylation, and may allow to further exploit the desired properties of this modification in different clinical contexts.
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spelling pubmed-92796682022-07-15 Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies Golay, Josée Andrea, Alain E. Cattaneo, Irene Front Immunol Immunology The presence of fucose on IgG1 Asn-297 N-linked glycan is the modification of the human IgG1 Fc structure with the most significant impact on FcɣRIII affinity. It also significantly enhances the efficacy of antibody dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells in vitro, induced by IgG1 therapeutic monoclonal antibodies (mAbs). The effect of afucosylation on ADCC or antibody dependent phagocytosis (ADCP) mediated by macrophages or polymorphonuclear neutrophils (PMN) is less clear. Evidence for enhanced efficacy of afucosylated therapeutic mAbs in vivo has also been reported. This has led to the development of several therapeutic antibodies with low Fc core fucose to treat cancer and inflammatory diseases, seven of which have already been approved for clinical use. More recently, the regulation of IgG Fc core fucosylation has been shown to take place naturally during the B-cell immune response: A decrease in α-1,6 fucose has been observed in polyclonal, antigen-specific IgG1 antibodies which are generated during alloimmunization of pregnant women by fetal erythrocyte or platelet antigens and following infection by some enveloped viruses and parasites. Low IgG1 Fc core fucose on antigen-specific polyclonal IgG1 has been linked to disease severity in several cases, such as SARS-CoV 2 and Dengue virus infection and during alloimmunization, highlighting the in vivo significance of this phenomenon. This review aims to summarize the current knowledge about human IgG1 Fc core fucosylation and its regulation and function in vivo, in the context of both therapeutic antibodies and the natural immune response. The parallels in these two areas are informative about the mechanisms and in vivo effects of Fc core fucosylation, and may allow to further exploit the desired properties of this modification in different clinical contexts. Frontiers Media S.A. 2022-06-30 /pmc/articles/PMC9279668/ /pubmed/35844552 http://dx.doi.org/10.3389/fimmu.2022.929895 Text en Copyright © 2022 Golay, Andrea and Cattaneo https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Immunology
Golay, Josée
Andrea, Alain E.
Cattaneo, Irene
Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies
title Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies
title_full Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies
title_fullStr Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies
title_full_unstemmed Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies
title_short Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies
title_sort role of fc core fucosylation in the effector function of igg1 antibodies
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279668/
https://www.ncbi.nlm.nih.gov/pubmed/35844552
http://dx.doi.org/10.3389/fimmu.2022.929895
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