Fab N-Glycosylation in IgG: Implications in Physiological and Pathological Immune Regulation

TL;DR

This paper reviews how Fab N-glycosylation in IgG affects immune regulation in health and disease, highlighting its structural diversity and functional roles.

Contribution

The paper provides a comprehensive review of Fab N-glycosylation's role in immune regulation, comparing it to IgG4 and discussing its implications in disease.

Findings

Fab N-glycosylation modulates antibody stability, half-life, and antigen-binding activity.

It plays roles in autoimmune diseases, pregnancy-induced tolerance, and tumor immune evasion.

Structural complexity and site variability hinder understanding of its functional impacts.

Abstract

Compared with classical Fc N-glycosylation, Fab N-glycosylation displays site heterogeneity and structural diversity. It contributes to immune regulation by modulating antibody stability, half-life, and antigen-binding activity, as well as by mediating blocking antibody effects. This review highlights the expression patterns and potential mechanisms of Fab N-glycosylated IgG in autoimmune diseases, pregnancy-induced immune tolerance, and tumor immune evasion, and discusses its structural and functional similarities to IgG4. Although Fab N-glycosylation plays an important role in both physiological and pathological conditions, the complexity of its glycan structures and variability in glycosylation sites hinder a precise understanding of its functional impacts. Clarifying these aspects is expected to emerge as a major focus in glycomics and antibody engineering research.

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