The role of differential IgG glycosylation in the interaction of antibodies with FcγRs in vivo

Abstract

Purpose of review: Immunoglobulin G (IgG) antibodies are centrally involved in pathogen clearance, tissue destruction and inflammation during autoimmune diseases, and have emerged as an important mediator of chronic organ rejection. Besides these pro-inflammatory activities, IgG antibodies can also have anti-inflammatory activities and are used to treat autoimmune disease and to prevent organ rejection in the form of high-dose intravenous immunoglobulin (IVIg) therapy. This review summarizes the mechanisms involved in these diverse activities of IgG.

Recent findings: Recent studies have highlighted the role of cellular receptors recognizing the antibody constant fragment (Fcγ-receptors, FcγR) for mediating IgG-dependent effector functions. In addition, the IgG-attached sugar moiety was identified as a molecular switch shifting IgG activity from a pro-inflammatory to an anti-inflammatory pathway. Besides the family of canonical FcγRs, specific Icam-3 grabbing nonintegrin-related 1 (SIGN-R1) and DC-SIGN were identified to recognize IgG glycoforms rich in sialic acid.

Summary: The identification of the IgG-attached sugar moiety as an important modulator of IgG activity makes it an attractive target to selectively potentiate either the pro-inflammatory or the anti-inflammatory activities of IgG. This finding will provide optimized IgG-based therapeutics to either enhance IgG-dependent tumor cell destruction or suppress IgG-dependent autoimmunity and organ rejection.