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Science 313 (5787): 670-673

Copyright © 2006 by the American Association for the Advancement of Science

Anti-Inflammatory Activity of Immunoglobulin G Resulting from Fc Sialylation

Yoshikatsu Kaneko,* Falk Nimmerjahn,* Jeffrey V. Ravetch{dagger}

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.

Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ravetch{at}rockefeller.edu


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Nephrol. Dial. Transplant. 22, 1301-1304
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Sialic Acid on Herpes Simplex Virus Type 1 Envelope Glycoproteins Is Required for Efficient Infection of Cells.
J. R. Teuton and C. R. Brandt (2007)
J. Virol. 81, 3731-3739
   Abstract »    Full Text »    PDF »
Lectins: Carbohydrate-specific Reagents and Biological Recognition Molecules.
N. Sharon (2007)
J. Biol. Chem. 282, 2753-2764
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The antiinflammatory activity of IgG: the intravenous IgG paradox.
F. Nimmerjahn and J. V. Ravetch (2007)
J. Exp. Med. 204, 11-15
   Abstract »    Full Text »    PDF »
N-Linked Glycosylation of Folded Proteins by the Bacterial Oligosaccharyltransferase..
M. Kowarik, S. Numao, M. F. Feldman, B. L. Schulz, N. Callewaert, E. Kiermaier, I. Catrein, and M. Aebi (2006)
Science 314, 1148-1150
   Abstract »    Full Text »    PDF »
Immunology. Sugar determines antibody activity..
D. R. Burton and R. A. Dwek (2006)
Science 313, 627-628
   Abstract »    Full Text »    PDF »

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