ArticleFrontiers in immunology2017
Decoding the Human Immunoglobulin G-Glycan Repertoire Reveals a Spectrum of Fc-Receptor- and Complement-Mediated-Effector Activities.
Article in Frontiers in immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 229 papers, 1 of them a synthesis that pooled it.
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Who cites it
229 citing papers in PubMed, 1 synthesis or guideline pooled it, 353 citations in OpenAlex.
- A systematic review of protein post-translational modifications in sepsis.Molecular biology reports · 2025Pooled it
- Article
- Longitudinal Profiling of IgG and IgA Glycosylation in Pregnancy Reveals Early Associations with BMI, Nulliparity and Conception Mode: The Rotterdam Periconception Cohort.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- IgG Glycosylation Patterns May Identify Distinct Clinical Trajectories in Fibromyalgia Patients: A Longitudinal Pilot Study.European journal of pain (London, England) · 2026Article
- Vaccination-first immune priming shapes a sustained mRNA vaccine-induced IgG4 class switch that associates with SARS-CoV-2 breakthrough infection risk.Scientific reports · 2026Article
- A Serum N-Glycan Ratio Associated With Disease Severity and Treatment Response in Psoriasis.The Journal of dermatology · 2026Article
- Glycosylation profile ofiScience · 2026Article
- Construction and validation of a glycosylation-related diagnostic model and immune characterization in lupus nephritis.Clinical rheumatology · 2026Article
- CSF-Compartmentalized Antibody Glycoprofiles in NMDAR Encephalitis Associate with Etiology and Functional Recovery.Annals of neurology · 2026Article
- Multi-factorial regulatory networks of placental antibody transfer by Fc receptors and maternal IgG Fc characteristics are modulated by clinical covariate profiles.bioRxiv : the preprint server for biology · 2026Article
- The association between plasma IgG N-glycosylation and viral encephalitis in children: a hospital-based case-control study.Italian journal of pediatrics · 2026Article
- Effect of ADCC-enhancing mutations on N-glycan profiles of human IgG1 antibodies.The Biochemical journal · 2026Article
- Antibody-Dependent Immune Complex Signaling and Inflammatory Cytokine Responses in Acute Febrile Illness: A Mechanistic Study in Arboviral and Leptospiral Infection.Open forum infectious diseases · 2026Article
- Antigen-specific IgG glycosylation profiles in hamsters and macaques following COVID-19 vaccination.iScience · 2026Article
- Site-specific profiling of structure and function of Igµ B cell receptor glycans.Nature communications · 2026Article
- Transplacental Antibody Transfer: Mechanisms, Pregnancy-Related Disruptions, and Emerging Experimental Models.Antibodies (Basel, Switzerland) · 2026Review
- Autoantibodies as Precision Tools in Connective Tissue Diseases: From Epiphenomenon to Endophenotype.Antibodies (Basel, Switzerland) · 2026Review
- Immunoglobulin GFrontiers in immunology · 2026Article
- Glycan Remodeling Technologies for Enhancing Antibody Function.Advances in experimental medicine and biology · 2026Review
- Differences in IgG Sialylation Distinguish Asymptomatic From Symptomatic Antinuclear Antibody-Positive Individuals.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
169 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycosylation of the immunoglobulin G (IgG)-Fc tail is required for binding to Fc-gamma receptors (FcγRs) and complement-component C1q. A variety of IgG1-glycoforms is detected in human sera. Several groups have found global or antigen-specific skewing of IgG glycosylation, for example in autoimmune diseases, viral infections, and alloimmune reactions. The IgG glycoprofiles seem to correlate with disease outcome. Additionally, IgG-glycan composition contributes significantly to Ig-based therapies, as for example IVIg in autoimmune diseases and therapeutic antibodies for cancer treatment. The effect of the different glycan modifications, especially of fucosylation, has been studied before. However, the contribution of the 20 individual IgG glycoforms, in which the combined effect of all 4 modifications, to the IgG function has never been investigated. Here, we combined six glyco-engineering methods to generate all 20 major human IgG1-glycoforms and screened their functional capacity for FcγR and complement activity. Bisection had no effect on FcγR or C1q-binding, and sialylation had no- or little effect on FcγR binding. We confirmed that hypo-fucosylation of IgG1 increased binding to FcγRIIIa and FcγRIIIb by ~17-fold, but in addition we showed that this effect could be further increased to ~40-fold for FcγRIIIa upon simultaneous hypo-fucosylation and hyper-galactosylation, resulting in enhanced NK cell-mediated antibody-dependent cellular cytotoxicity. Moreover, elevated galactosylation and sialylation significantly increased (independent of fucosylation) C1q-binding, downstream complement deposition, and cytotoxicity. In conclusion, fucosylation and galactosylation are primary mediators of functional changes in IgG for FcγR- and complement-mediated effector functions, respectively, with galactose having an auxiliary role for FcγRIII-mediated functions. This knowledge could be used not only for glycan profiling of clinically important (antigen-specific) IgG but also to optimize therapeutic antibody applications.
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