Anti-Inflammatory Activity of Immunoglobulin G Resulting from Fc Sialylation

  title={Anti-Inflammatory Activity of Immunoglobulin G Resulting from Fc Sialylation},
  author={Yoshikatsu Kaneko and F. Nimmerjahn and Jeffrey V. Ravetch},
  pages={670 - 673}
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… 

Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity.

Induction of IgG Fc sialylation of human monoclonal IgG1 molecules impairs their efficacy to induce complement-mediated cytotoxicity (CDC), an FcγR-independent mechanism by which Fc-sialylated glycovariants might limit proinflammatory IgG effector functions.

A Novel Role for the IgG Fc Glycan: The Anti-inflammatory Activity of Sialylated IgG Fcs

Sialylated IgG Fcs initiate an anti-inflammatory cascade through the lectin receptor SIGN-R1 or DC-SIGN, which leads to upregulated surface expression of the inhibitory FcR, FcγRIIb, on inflammatory cells, thereby attenuating autoantibody-initiated inflammation.

The pro and anti-inflammatory activities of immunoglobulin G

How one class of molecules can have such opposing functions will be the major focus of this review.

Novel Fc receptors mediating the anti-inflammatory properties of IgG

A novel antibody receptor specific for sialylated Fc has been identified as well as the initial step that is triggered by IVIG to suppress inflammation.

The role of sialic acid as a modulator of the anti-inflammatory activity of IgG

This review will focus on sialic acid residues as a modulator of the anti-inflammatory activity of IgG, and provide an overview of situations where serum IgG glycosylation and sialylation is altered and which molecular and cellular pathways may be involved in this immunomodulatory pathway.

Structural characterization of anti-inflammatory immunoglobulin G Fc proteins.

The therapeutic potential of sialylated Fc domains of human IgG

The development of molecular scaffolds based on the crystallizable fragment (Fc) region of immunoglobulin (Ig) G that deliver high-avidity binding to innate immune receptors, including sialic acid-dependent receptors are described.

Novel roles for the IgG Fc glycan

The N‐linked glycans on the IgG Fc are absolutely required for initiating and suppressing inflammation, and the Fc glycan requirements to initiate and suppress inflammation will be discussed herein.

Aglycosylated immunoglobulin G1 variants productively engage activating Fc receptors

Aglycosylated Fc domain variants that maintain engagement to Fcγ receptors, both in vitro and in vivo, are reported, demonstrating that Fc glycosylation is not strictly required for the activation of immune cells by IgG.

Low-affinity Fcγ receptors, autoimmunity and infection

The role of the low-affinity F cγRs in a balanced immune response and how perturbations in FcγR function result in susceptibility to infection or autoimmunity are discussed.



Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor.

Protection was associated with the ability of IVIG administration to induce surface expression of FcgammaRIIB on splenic macrophages, and modulation of inhibitory signaling is a potent therapeutic strategy for attenuating autoantibody-triggered inflammatory diseases.

Divergent Immunoglobulin G Subclass Activity Through Selective Fc Receptor Binding

The mechanism underlying this long-standing observation of subclass dominance in function is provided by the differential affinities of IgG subclasses for specific activating IgG Fc receptors compared with their affinITIES for the inhibitory IgGFc receptor.

Changes in the galactose content of IgG during humoral immune responses.

If specific pathogen free CBA/Ca mice are transferred from a sterile to a conventional environment, their levels of total serum IgG rise whereas the degree of IgG galactosylation falls, and it is shown that such changes in IgG glycosylation occur during non-pathological humoral immune responses.

Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors

The results establish the significance of specific IgG subclasses and their cognate FcγRs in renal disease and indicate that reduced F cγRIV expression alone is insufficient to protect animals from pathogenic IgG2b immune complexes.

Autoantibody activity of IgG rheumatoid factor increases with decreasing levels of galactosylation and sialylation.

The decreases in galactosylation and sialylation of oligosaccharides in IgGRF correlated well with the increase in RF activity, which could contribute to the understanding of the mechanisms of IgG-IgG complex formation and the pathogenicity of these complexes in RA patients.

Agalactosyl glycoforms of IgG autoantibodies are pathogenic.

It is demonstrated that passive transfer of an acute synovitis in T-cell-primed mice can be enhanced by using IgG containing autoantibodies to type II collagen when the antibodies are present as the agalactosyl glycoform.

Molecular basis for immune complex recognition: a comparison of Fc-receptor structures.

The obtained models are consistent with the observed biochemical data and may explain the observed specificity and affinities of Fcgamma-receptors.