ArticleJournal of molecular biology2014
Structural determinants of unique properties of human IgG4-Fc.
Article in Journal of molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- A systematic review and meta-analysis of HLA class II associations in patients with IgG4 autoimmunity.Scientific reports · 2022Pooled it
- CLEC5A/TLR2 bispecific antibody suppresses dengue virus-induced pro-inflammatory cytokines production from macrophages.Journal of biomedical science · 2026Article
- Humoral immunity in pancreatic cancer: B-cell heterogeneity, regulatory networks, and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- A real-world study of adverse event profiles associated with the four key components of antibody-drug conjugates based on the FAERS database.Frontiers in pharmacology · 2026Article
- Autoimmune nodopathy associated with Sjögren's disease and nephrotic syndrome: a case report and literature review.Frontiers in immunology · 2026Review
- Clinical Spectrum, Pathology, and Mechanisms of Anti-LGI4 Antibody-Positive Autoimmune Nodopathy.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- The Crystal Structure of Human IgD-Fc Reveals Unexpected Differences With Other Antibody Isotypes.Proteins · 2025Article
- Type 2 immunity in allergic diseases.Cellular & molecular immunology · 2025Review
- IgG4 glycosylation contributes to the pathogenesis of IgG4 Hashimoto's thyroiditis via the complement pathway.European thyroid journal · 2024Article
- CG001, a C3b-targeted complement inhibitor, blocks 3 complement pathways: development and preclinical evaluation.Blood advances · 2024Article
- Article
- Using atomistic solution scattering modelling to elucidate the role of the Fc glycans in human IgG4.PloS one · 2024Article
- Immunoglobulin G4 in primary Sjögren's syndrome and IgG4-related disease - connections and dissimilarities.Frontiers in immunology · 2024Review
- The unique properties of IgG4 and its roles in health and disease.Nature reviews. Immunology · 2023Review
- A CD64/FcγRI-mediated mechanism hijacks PD-1 from PD-L1/2 interaction and enhances anti-PD-1 functional recovery of exhausted T cells.Frontiers in immunology · 2023Article
- Factors affecting IgG4-mediated complement activation.Frontiers in immunology · 2023Article
- Impact of structural modifications of IgG antibodies on effector functions.Frontiers in immunology · 2023Review
- Decreasing hydrophobicity or shielding hydrophobic areas of CH2 attenuates low pH-induced IgG4 aggregation.Frontiers in bioengineering and biotechnology · 2023Article
- Quantifying In Situ Structural Stabilities of Human Blood Plasma Proteins Using a Novel Iodination Protein Stability Assay.Journal of proteome research · 2022Article
- Fruquintinib in Combination With PD-1 Inhibitors in Patients With Refractory Non-MSI-H/pMMR Metastatic Colorectal Cancer: A Real-World Study in China.Frontiers in oncology · 2022Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Human IgG4, normally the least abundant of the four subclasses of IgG in serum, displays a number of unique biological properties. It can undergo heavy-chain exchange, also known as Fab-arm exchange, leading to the formation of monovalent but bispecific antibodies, and it interacts poorly with FcγRII and FcγRIII, and complement. These properties render IgG4 relatively "non-inflammatory" and have made it a suitable format for therapeutic monoclonal antibody production. However, IgG4 is also known to undergo Fc-mediated aggregation and has been implicated in auto-immune disease pathology. We report here the high-resolution crystal structures, at 1.9 and 2.35 Å, respectively, of human recombinant and serum-derived IgG4-Fc. These structures reveal conformational variability at the CH3-CH3 interface that may promote Fab-arm exchange, and a unique conformation for the FG loop in the CH2 domain that would explain the poor FcγRII, FcγRIII and C1q binding properties of IgG4 compared with IgG1 and -3. In contrast to other IgG subclasses, this unique conformation folds the FG loop away from the CH2 domain, precluding any interaction with the lower hinge region, which may further facilitate Fab-arm exchange by destabilisation of the hinge. The crystals of IgG4-Fc also display Fc-Fc packing contacts with very extensive interaction surfaces, involving both a consensus binding site in IgG-Fc at the CH2-CH3 interface and known hydrophobic aggregation motifs. These Fc-Fc interactions are compatible with intact IgG4 molecules and may provide a model for the formation of aggregates of IgG4 that can cause disease pathology in the absence of antigen.
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What OpenQuestion holds
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.