Cargando…

Current understanding of IgA antibodies in the pathogenesis of IgA nephropathy

Immunoglobulin A (IgA) is the most abundant isotype of antibodies, provides a first line of defense at mucosal surfaces against pathogens, and thereby contributes to mucosal homeostasis. IgA is generally considered as a non-inflammatory antibody because of its main function, neutralizing pathogenic...

Descripción completa

Detalles Bibliográficos
Autores principales: Nihei, Yoshihito, Suzuki, Hitoshi, Suzuki, Yusuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10126238/
https://www.ncbi.nlm.nih.gov/pubmed/37114051
http://dx.doi.org/10.3389/fimmu.2023.1165394
_version_ 1785030194867732480
author Nihei, Yoshihito
Suzuki, Hitoshi
Suzuki, Yusuke
author_facet Nihei, Yoshihito
Suzuki, Hitoshi
Suzuki, Yusuke
author_sort Nihei, Yoshihito
collection PubMed
description Immunoglobulin A (IgA) is the most abundant isotype of antibodies, provides a first line of defense at mucosal surfaces against pathogens, and thereby contributes to mucosal homeostasis. IgA is generally considered as a non-inflammatory antibody because of its main function, neutralizing pathogenic virus or bacteria. Meanwhile, IgA can induce IgA-mediated diseases, such as IgA nephropathy (IgAN) and IgA vasculitis. IgAN is characterized by the deposition of IgA and complement C3, often with IgG and/or IgM, in the glomerular mesangial region, followed by mesangial cell proliferation and excessive synthesis of extracellular matrix in glomeruli. Almost half a century has passed since the first report of patients with IgAN; it remains debatable about the mechanism how IgA antibodies selectively bind to mesangial region—a hallmark of IgAN—and cause glomerular injuries in IgAN. Previous lectin- and mass-spectrometry-based analysis have revealed that IgAN patients showed elevated serum level of undergalactosylated IgA1 in O-linked glycans of its hinge region, called galactose-deficient IgA1 (Gd-IgA1). Thereafter, numerous studies have confirmed that the glomerular IgA from IgAN patients are enriched with Gd-IgA1; thus, the first hit of the current pathogenesis of IgAN has been considered to increase circulating levels of Gd-IgA1. Recent studies, however, demonstrated that this aberrant glycosylation alone is not sufficient to disease onset and progression, suggesting that several additional factors are required for the selective deposition of IgA in the mesangial region and induce nephritis. Herein, we discuss the current understanding of the characteristics of pathogenic IgA and its mechanism of inducing inflammation in IgAN.
format Online
Article
Text
id pubmed-10126238
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-101262382023-04-26 Current understanding of IgA antibodies in the pathogenesis of IgA nephropathy Nihei, Yoshihito Suzuki, Hitoshi Suzuki, Yusuke Front Immunol Immunology Immunoglobulin A (IgA) is the most abundant isotype of antibodies, provides a first line of defense at mucosal surfaces against pathogens, and thereby contributes to mucosal homeostasis. IgA is generally considered as a non-inflammatory antibody because of its main function, neutralizing pathogenic virus or bacteria. Meanwhile, IgA can induce IgA-mediated diseases, such as IgA nephropathy (IgAN) and IgA vasculitis. IgAN is characterized by the deposition of IgA and complement C3, often with IgG and/or IgM, in the glomerular mesangial region, followed by mesangial cell proliferation and excessive synthesis of extracellular matrix in glomeruli. Almost half a century has passed since the first report of patients with IgAN; it remains debatable about the mechanism how IgA antibodies selectively bind to mesangial region—a hallmark of IgAN—and cause glomerular injuries in IgAN. Previous lectin- and mass-spectrometry-based analysis have revealed that IgAN patients showed elevated serum level of undergalactosylated IgA1 in O-linked glycans of its hinge region, called galactose-deficient IgA1 (Gd-IgA1). Thereafter, numerous studies have confirmed that the glomerular IgA from IgAN patients are enriched with Gd-IgA1; thus, the first hit of the current pathogenesis of IgAN has been considered to increase circulating levels of Gd-IgA1. Recent studies, however, demonstrated that this aberrant glycosylation alone is not sufficient to disease onset and progression, suggesting that several additional factors are required for the selective deposition of IgA in the mesangial region and induce nephritis. Herein, we discuss the current understanding of the characteristics of pathogenic IgA and its mechanism of inducing inflammation in IgAN. Frontiers Media S.A. 2023-04-11 /pmc/articles/PMC10126238/ /pubmed/37114051 http://dx.doi.org/10.3389/fimmu.2023.1165394 Text en Copyright © 2023 Nihei, Suzuki and Suzuki 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
Nihei, Yoshihito
Suzuki, Hitoshi
Suzuki, Yusuke
Current understanding of IgA antibodies in the pathogenesis of IgA nephropathy
title Current understanding of IgA antibodies in the pathogenesis of IgA nephropathy
title_full Current understanding of IgA antibodies in the pathogenesis of IgA nephropathy
title_fullStr Current understanding of IgA antibodies in the pathogenesis of IgA nephropathy
title_full_unstemmed Current understanding of IgA antibodies in the pathogenesis of IgA nephropathy
title_short Current understanding of IgA antibodies in the pathogenesis of IgA nephropathy
title_sort current understanding of iga antibodies in the pathogenesis of iga nephropathy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10126238/
https://www.ncbi.nlm.nih.gov/pubmed/37114051
http://dx.doi.org/10.3389/fimmu.2023.1165394
work_keys_str_mv AT niheiyoshihito currentunderstandingofigaantibodiesinthepathogenesisofiganephropathy
AT suzukihitoshi currentunderstandingofigaantibodiesinthepathogenesisofiganephropathy
AT suzukiyusuke currentunderstandingofigaantibodiesinthepathogenesisofiganephropathy