ArticleProceedings of the National Academy of Sciences of the United States of America2015
Protection in antibody- and T cell-mediated autoimmune diseases by antiinflammatory IgG Fcs requires type II FcRs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Glycosylation of Immunoglobulin G Associates With Clinical Features of Inflammatory Bowel Diseases.Gastroenterology · 2018Pooled it
- Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy.Cell reports. Medicine · 2022Trial
- Overview of T-cell subsets and related cytokines in Kawasaki disease.Pediatric research · 2026Review
- Enhancing IgG fragment crystallizable sialylation improves the therapeutic activity of IL-23 cytokine blockade.JCI insight · 2026Article
- Intravenous immunoglobulin remodels innate immune cell communication and induces differential autophagy pathways in Kawasaki disease.Frontiers in immunology · 2026Article
- More Than Just Antinuclear Antibodies: IgG Sialylation May Tip the Balance in Autoimmunity.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- A recombinant IgG1 Fc-domain protein ameliorates inflammatory demyelinating peripheral neuropathy.Frontiers in immunology · 2026Article
- The role and potential mechanism of immunoglobulin G N-glycosylation in gastrointestinal tumors.Medical molecular morphology · 2025Review
- The anti-inflammatory activity of IgG is enhanced by co-engagement of type I and II Fc receptors.Science (New York, N.Y.) · 2025Article
- Aberrant Glycosylation of IgG in Children With Active Lupus Nephritis Alters Podocyte Metabolism and Causes Podocyte Injury.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Therapeutic effect of galactosyltransferase- and sialyltransferase-encoding mRNA in rheumatoid arthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Molecular determinants of sialylated IgG anti-inflammatory activity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Effectiveness of Additional Immunosuppressive Drugs for Corticosteroid-refractory Immune Checkpoint Inhibitor-induced Myocarditis: Two Case Reports.Internal medicine (Tokyo, Japan) · 2025Article
- Soluble Factors and Mechanisms Regulated by Sialylated IgG Signaling.Immunological reviews · 2025Review
- Article
- Role of Antibody Glycosylation in Health, Disease, and Therapy.Handbook of experimental pharmacology · 2025Review
- Emerging treatment landscape for Guillain-Barré Syndrome (GBS): what's new?Expert opinion on investigational drugs · 2024Review
- An engineered immunomodulatory IgG1 Fc suppresses autoimmune inflammation through pathways shared with i.v. immunoglobulin.The Journal of clinical investigation · 2024Article
- Article
- Production of recombinant human IgG1 Fc with beneficial N-glycosylation pattern for anti-inflammatory activity using genome-edited chickens.Communications biology · 2023Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The antiinflammatory activity of intravenous immunoglobulin (IVIG) is dependent on the presence of sialic acid in the core IgG fragment crystallizable domain (Fc) glycan, resulting in increased conformational flexibility of the CH2 domain with corresponding modulation of Fc receptor (FcR) binding specificity from type I to type II receptors. Sialylated IgG Fc (sFc) increases the activation threshold of innate effector cells to immune complexes by stimulating the up-regulation of the inhibitory receptor FcγRIIB. We have found that the structural alterations induced by sialylation can be mimicked by specific amino acid modifications to the CH2 domain. An IgG Fc variant with a point mutation at position 241 (F→A) exhibits antiinflammatory activity even in the absence of sialylation. F241A and sFc protect mice from arthritis in the K/BxN-induced model and, in the T cell-mediated experimental autoimmune encephalomyelitis (EAE) mouse model, suppress disease by specifically activating regulatory T cells (Treg cells). Protection by these antiinflammatory Fcs in both antibody- and T cell-mediated autoimmune diseases required type II FcRs and the induction of IL-33. These results further clarify the mechanism of action of IVIG in both antibody- and T cell-mediated inflammatory diseases and demonstrate that Fc variants that mimic the structural alterations induced by sialylation, such as F241A, can be promising therapeutic candidates for the treatment of various autoimmune disorders.
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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.