Anti-Inflammatory Activity of Immunoglobulin G Resulting from Fc Sialylation

TLDR

IgG mediates pro‑ and anti‑inflammatory activities via its Fc fragment binding distinct Fcγ receptors, with some Fc‑FcγR interactions driving pro‑inflammatory immune complex and cytotoxic antibody responses. The study aims to demonstrate that IgG Fc pro‑ and anti‑inflammatory properties arise from differential sialylation of its core polysaccharide. IgG gains anti‑inflammatory activity when its Fc is sialylated, a modification that diminishes during antigen‑specific immune responses. Therapeutic IgG and its Fc fragments are anti‑inflammatory because Fc sialylation confers this activity, a modification that is reduced during antigen‑specific responses, suggesting sialylation switches IgG from innate anti‑inflammatory to adaptive pro‑inflammatory functions.

Abstract

Immunoglobulin G (IgG) mediates pro- and anti-inflammatory activities through the engagement of its Fc fragment (Fc) with distinct Fcg receptors (FcgRs). One class of Fc-FcgR interactions generates pro-inflammatory effects of immune complexes and cytotoxic antibodies. In contrast, therapeutic intravenous gamma globulin and its Fc fragments are anti-inflammatory. We show here that these distinct properties of the IgG Fc result from differential sialylation of the Fc core polysaccharide. IgG acquires anti-inflammatory properties upon Fc sialylation, which is reduced upon the induction of an antigen-specific immune response. This differential sialylation may provide a switch from innate anti-inflammatory activity in the steady state to generating adaptive pro-inflammatory effects upon antigenic challenge.