Cited by 849Monoclonal and Polyclonal Antibodies ResearchGlycosylation and Glycoproteins ResearchT-cell and B-cell Immunology

Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc

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Anthony, Robert M., Nimmerjahn, Falk, Ashline, David J., Reinhold, Vernon N., Paulson, James C., Ravetch, Jeffrey V.·2008·Science

Abstract

It is well established that high doses of monomeric immunoglobulin G (IgG) purified from pooled human plasma [intravenous immunoglobulin (IVIG)] confer anti-inflammatory activity in a variety of autoimmune settings. However, exactly how those effects are mediated is not clear because of the heterogeneity of IVIG. Recent studies have demonstrated that the anti-inflammatory activity of IgG is completely dependent on sialylation of the N-linked glycan of the IgG Fc fragment. Here we determine the precise glycan requirements for this anti-inflammatory activity, allowing us to engineer an appropriate IgG1 Fc fragment, and thus generate a fully recombinant, sialylated IgG1 Fc with greatly enhanced potency. This therapeutic molecule precisely defines the biologically active component of IVIG and helps guide development of an IVIG replacement with improved activity and availability.

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Crossref · 10.1126/science.1154315

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  • Galactose is required for sialylation with NeuAc, which can improve solubility, anti-inflammatory activity, thermal stability and serum half-life of mAbs.

    “On the other hand, galactose is required for sialylation with N-acetylneuraminic acid (NeuAc), which in turn can improve the solubility, anti-inflammatory activity, thermal stability and serum half-life of mAbs [8,23–26].”

    From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [24]

    The section labeled Abstract (page not provided) describes adding galactose before sialylating IgG Fc glycans and reports anti-inflammatory activity for the 2,6-sialylated Fc. It does not report improved solubility, thermal stability, or serum half-life of mAbs. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • α2,6-linked NeuAc (main sialic acid linkage in human IgG) is solely required for the anti-inflammatory activity of IgG mediated by non-canonical IgG-Fc receptors.

    “it is the α2,6-linked NeuAc (main sialic acid linkage in human IgG) that is solely required for the anti-inflammatory activity of IgG mediated by non-canonical IgG-Fc receptors [24].”

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Research works printed but not linked: 2

  1. [11]Kitagawa H, Paulson JC. J Biol Chem. 1994;269:17872. [PubMed] [Google Scholar]
  2. [27]Crocker PR, Werb Z, Gordon S, Bainton DF. Blood. 1990;76:1131. [PubMed] [Google Scholar]

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Authors
Anthony, R. M., Nimmerjahn, F., Ashline, D. J., Reinhold, V. N., Paulson, J. C., & Ravetch, J. V.
Affiliations
Scripps Research Institute (US)
Corresponding author
Ravetch, Jeffrey V.
Venue
Science
Published
2008-04-18
Volume
320
Issue
5874
Pages
373-376
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2051666192
Cited by
849
References
34
Citations by year
2026: 19 · 2025: 32 · 2024: 29 · 2023: 37 · 2022: 39 · 2021: 39 · 2020: 50 · 2019: 39 · 2018: 45 · 2017: 46 · 2016: 66 · 2015: 58 · 2014: 58 · 2013: 58 · 2012: 68
FWCI
42.36
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r01gm060938-10)
  • National Institute of General Medical Sciences (R01GM054045, R01-GM060938, GM60938)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
intravenous immunoglobulin, anti-inflammatory activity, IgG Fc fragment, sialylation, N-glycans, glycan engineering, autoimmune disease
MeSH terms
Animals, Anti-Inflammatory Agents, Non-Steroidal, Arthritis, Experimental, Autoimmune Diseases, Carbohydrate Conformation, Galactose, Glycosylation, Humans, Immunoglobulin G, Immunoglobulin Fc Fragments, Mice, Inbred C57BL, Polysaccharides, Receptors, Fc, Recombinant Proteins, Purpura, Thrombocytopenic, Idiopathic, Mice, Inbred NOD, Immunoglobulins, Intravenous, N-Acetylneuraminic Acid, Mice

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