title: The role of differential IgG glycosylation in the interaction of antibodies with FcγRs in vivo.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Anthony
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism*; D006023:Glycoproteins
chemical_list: D000906:Antibodies; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D017452:Receptors, IgG; C046179:glycosylated IgG; D006023:Glycoproteins