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Review
. 2022 Sep 27:10:974854.
doi: 10.3389/fchem.2022.974854. eCollection 2022.

Advances in IgA glycosylation and its correlation with diseases

Li Ding  1 , Xiangqin Chen  1 , Hongwei Cheng  1 , Tiantian Zhang  1 , Zheng Li  1
Affiliations
Review

Advances in IgA glycosylation and its correlation with diseases

Li Ding et al. Front Chem. .

Abstract

Immunoglobulin A (IgA) is the most abundant immunoglobulin synthesized in the human body. It has the highest concentration in the mucosa and is second only to IgG in serum. IgA plays an important role in mucosal immunity, and is the predominant antibody used to protect the mucosal surface from pathogens invasion and to maintain the homeostasis of intestinal flora. Moreover, The binding IgA to the FcαRI (Fc alpha Receptor I) in soluble or aggregated form can mediate anti- or pro- inflammatory responses, respectively. IgA is also known as one of the most heavily glycosylated antibodies among human immunoglobulins. The glycosylation of IgA has been shown to have a significant effect on its immune function. Variation in the glycoform of IgA is often the main characteration of autoimmune diseases such as IgA nephropathy (IgAN), IgA vasculitis (IgAV), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). However, compared with the confirmed glycosylation function of IgG, the pathogenic mechanism of IgA glycosylation involved in related diseases is still unclear. This paper mainly summarizes the recent reports on IgA's glycan structure, its function, its relationship with the occurrence and development of diseases, and the potential application of glycoengineered IgA in clinical antibody therapeutics, in order to provide a potential reference for future research in this field.

Keywords: IgA; antibody; glycosylation; immunoglobulin; therapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic diagram of the process of SIgA formation by mIgA and its glycosylation sites. IgA monomers (A,B) present in the mucosal plasma cells can form dimmers through the J-chain. The dIgA is then transported across the epithelium by binding to pIgR. At the luminal side, dIgA is released from the pIgR, and a part of the receptor (SC) remains attached to dIgA to form SIgA (C,D). (Davis et al., 2020; van Gool and van Egmond, 2020).
FIGURE 2
FIGURE 2
The O-glycosylation sites and glycan structures in human serum IgA1. (A) Boxed and numbered amino acids indicate the sites of attachment of O-linked glycans (CHO: carbohydrate) in the hinge region. (B) The core structures of O-glycans on human IgA1 are composed of GalNAc or GalNAcβ-1,3-Gal. Both of them can be modificated by Sia in different linkages (formula image: GalNAc; formula image: Gal; formula image: Sia) (Novak et al., 2000; Novak et al., 2018; Hansen et al., 2021).
See this image and copyright information in PMC

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