ArticleProceedings of the National Academy of Sciences of the United States of America2008
Identification of a receptor required for the anti-inflammatory activity of IVIG.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 279 papers.
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Who cites it
279 citing papers in PubMed, 528 citations in OpenAlex.
- High-throughput characterization of the functional impact of IgG Fc glycan aberrancy in juvenile idiopathic arthritis.Glycobiology · 2017Trial
- Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity.The Journal of clinical investigation · 2015Trial
- Immunoglobulin-mediated immune dysregulation in recurrent pregnancy loss: mechanisms, biomarkers, and therapeutic perspectives.Immunologic research · 2026Review
- Inhibiting glycan degradation prevents HIV-induced inflammaging and cognitive impairment.Med (New York, N.Y.) · 2026Article
- IgG Glycosylation Analysis in Patients with Ring14 Syndrome Unveils Novel Pathomechanisms and New Therapy Perspectives.Biomolecules · 2026Article
- Fc-engineered antibodies enhance protection against SARS-CoV-2 lung infection and inflammation.mBio · 2026Article
- Pre-intervention with intravenous immunoglobulin reverses the immunogenic clearance of PEGylated nanomedicines.Nature biomedical engineering · 2026Article
- IgG N-Glycosylation During Atorvastatin Therapy After Acute Coronary Syndrome is Associated with LDL Cholesterol Reduction.Journal of clinical medicine · 2026Article
- Article
- Autoantibodies as Precision Tools in Connective Tissue Diseases: From Epiphenomenon to Endophenotype.Antibodies (Basel, Switzerland) · 2026Review
- A recombinant IgG1 Fc-domain protein ameliorates inflammatory demyelinating peripheral neuropathy.Frontiers in immunology · 2026Article
- Inhibiting Glycan Degradation Prevents HIV-Induced Inflammaging and Cognitive Impairment.bioRxiv : the preprint server for biology · 2025Article
- The anti-inflammatory activity of IgG is enhanced by co-engagement of type I and II Fc receptors.Science (New York, N.Y.) · 2025Article
- Estrogen Modulation of B Cell Immunity: Implications for HIV Control and Therapeutic Strategies.Comprehensive physiology · 2025Review
- Therapeutic effect of galactosyltransferase- and sialyltransferase-encoding mRNA in rheumatoid arthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Glycomics in Human Diseases and Its Emerging Role in Biomarker Discovery.Biomedicines · 2025Review
- Recombinant IgG1 Fc-μTP-L309C Ameliorates Endogenous Rheumatoid Arthritis in the K/BxN Mouse Model by Decreasing Th1 and Th17 Cells in the Spleen, Lymph Nodes and Joint and Increasing T Regulatory Cells and IL-10 in the Joint.Journal of clinical medicine · 2025Article
- Molecular determinants of sialylated IgG anti-inflammatory activity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Glycosylation as an intricate post-translational modification process takes part in glycoproteins related immunity.Cell communication and signaling : CCS · 2025Review
- Beyond the Toll-Like Receptor 4. Structure-Dependent Lipopolysaccharide Recognition Systems: How far are we?ChemMedChem · 2025Review
219 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anti-inflammatory activity of intravenous Ig (IVIG) results from a minor population of the pooled IgG molecules that contains terminal alpha2,6-sialic acid linkages on their Fc-linked glycans. These anti-inflammatory properties can be recapitulated with a fully recombinant preparation of appropriately sialylated IgG Fc fragments. We now demonstrate that these sialylated Fcs require a specific C-type lectin, SIGN-R1, (specific ICAM-3 grabbing non-integrin-related 1) expressed on macrophages in the splenic marginal zone. Splenectomy, loss of SIGN-R1(+) cells in the splenic marginal zone, blockade of the carbohydrate recognition domain (CRD) of SIGN-R1, or genetic deletion of SIGN-R1 abrogated the anti-inflammatory activity of IVIG or sialylated Fc fragments. Although SIGN-R1 has not previously been shown to bind to sialylated glycans, we demonstrate that it preferentially binds to 2,6-sialylated Fc compared with similarly sialylated, biantennary glycoproteins, thus suggesting that a specific binding site is created by the sialylation of IgG Fc. A human orthologue of SIGN-R1, DC-SIGN, displays a similar binding specificity to SIGN-R1 but differs in its cellular distribution, potentially accounting for some of the species differences observed in IVIG protection. These studies thus identify an antibody receptor specific for sialylated Fc, and present the initial step that is triggered by IVIG to suppress inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.