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Recapitulation of IVIG Anti-Inflammatory Activity with a Recombinant IgG Fc
Open accessAbstract
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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“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]
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“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].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [24]
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Metadata
- 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
- PMC
- PMC2409116
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
- Life Sciences › Immunology and Microbiology › Immunology › 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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