Role of IgG4 Antibodies in Human Health and Disease

Immunoglobulin G4 (IgG4), a unique subclass of IgG antibodies, plays diverse roles in human health and disease. Its distinct features, such as Fab-arm exchange and specific mutations, confer reduced effector functions compared to other IgG subclasses. In health, IgG4 responses contribute to immune t...

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Main Authors: Li-li Shi, Peng Xiong, Minglin Yang, Ozge Ardicli, Stephan Raphael Schneider, Anders Boutrup Funch, Ayca Kiykim, Juan Lopez, Cezmi A. Akdis, Mübeccel Akdis
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/9/639
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author Li-li Shi
Peng Xiong
Minglin Yang
Ozge Ardicli
Stephan Raphael Schneider
Anders Boutrup Funch
Ayca Kiykim
Juan Lopez
Cezmi A. Akdis
Mübeccel Akdis
author_facet Li-li Shi
Peng Xiong
Minglin Yang
Ozge Ardicli
Stephan Raphael Schneider
Anders Boutrup Funch
Ayca Kiykim
Juan Lopez
Cezmi A. Akdis
Mübeccel Akdis
author_sort Li-li Shi
collection DOAJ
description Immunoglobulin G4 (IgG4), a unique subclass of IgG antibodies, plays diverse roles in human health and disease. Its distinct features, such as Fab-arm exchange and specific mutations, confer reduced effector functions compared to other IgG subclasses. In health, IgG4 responses contribute to immune tolerance, particularly in the context of allergen-specific immunotherapy (AIT), where they can mediate tolerance to environmental antigens, inhibit IgE-dependent mast cell degranulation, and compete with IgE for allergen binding. This helps in attenuating allergic symptoms and is associated with increased levels of allergen-specific IgG4. However, in disease scenarios, the role of IgG4 is complex. IgG4 lacks complement fixation and, thus, shows a reduced ability to activate immune effector pathways, it was initially thought to be protective against autoimmune diseases. However, emerging evidence suggests that it can contribute to pathology. For instance, IgG4 autoantibodies against specific antigens can aggravate conditions in certain autoimmune disorders. In some cancers, it may play a role in immune evasion, with higher levels correlating with poor patient survival, albeit in others, its exact function remains elusive. Overall, understanding the precise role of IgG4 in various physiological and pathological conditions is crucial for developing targeted therapeutic strategies and improving patient outcomes.
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spelling doaj-art-3f122ac461c64fba8e3c049c1eb85e7e2025-08-20T02:58:47ZengMDPI AGCells2073-44092025-04-0114963910.3390/cells14090639Role of IgG4 Antibodies in Human Health and DiseaseLi-li Shi0Peng Xiong1Minglin Yang2Ozge Ardicli3Stephan Raphael Schneider4Anders Boutrup Funch5Ayca Kiykim6Juan Lopez7Cezmi A. Akdis8Mübeccel Akdis9Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, SwitzerlandSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, SwitzerlandSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, SwitzerlandSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, SwitzerlandSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, SwitzerlandSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, SwitzerlandSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, SwitzerlandSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, SwitzerlandSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, SwitzerlandSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, SwitzerlandImmunoglobulin G4 (IgG4), a unique subclass of IgG antibodies, plays diverse roles in human health and disease. Its distinct features, such as Fab-arm exchange and specific mutations, confer reduced effector functions compared to other IgG subclasses. In health, IgG4 responses contribute to immune tolerance, particularly in the context of allergen-specific immunotherapy (AIT), where they can mediate tolerance to environmental antigens, inhibit IgE-dependent mast cell degranulation, and compete with IgE for allergen binding. This helps in attenuating allergic symptoms and is associated with increased levels of allergen-specific IgG4. However, in disease scenarios, the role of IgG4 is complex. IgG4 lacks complement fixation and, thus, shows a reduced ability to activate immune effector pathways, it was initially thought to be protective against autoimmune diseases. However, emerging evidence suggests that it can contribute to pathology. For instance, IgG4 autoantibodies against specific antigens can aggravate conditions in certain autoimmune disorders. In some cancers, it may play a role in immune evasion, with higher levels correlating with poor patient survival, albeit in others, its exact function remains elusive. Overall, understanding the precise role of IgG4 in various physiological and pathological conditions is crucial for developing targeted therapeutic strategies and improving patient outcomes.https://www.mdpi.com/2073-4409/14/9/639IgG4immune toleranceallergen-specific immunotherapy (AIT)autoimmune diseaseallergic diseasechronic infection
spellingShingle Li-li Shi
Peng Xiong
Minglin Yang
Ozge Ardicli
Stephan Raphael Schneider
Anders Boutrup Funch
Ayca Kiykim
Juan Lopez
Cezmi A. Akdis
Mübeccel Akdis
Role of IgG4 Antibodies in Human Health and Disease
Cells
IgG4
immune tolerance
allergen-specific immunotherapy (AIT)
autoimmune disease
allergic disease
chronic infection
title Role of IgG4 Antibodies in Human Health and Disease
title_full Role of IgG4 Antibodies in Human Health and Disease
title_fullStr Role of IgG4 Antibodies in Human Health and Disease
title_full_unstemmed Role of IgG4 Antibodies in Human Health and Disease
title_short Role of IgG4 Antibodies in Human Health and Disease
title_sort role of igg4 antibodies in human health and disease
topic IgG4
immune tolerance
allergen-specific immunotherapy (AIT)
autoimmune disease
allergic disease
chronic infection
url https://www.mdpi.com/2073-4409/14/9/639
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