ArticleProceedings of the National Academy of Sciences of the United States of America2019
Insights into IgM-mediated complement activation based on in situ structures of IgM-C1-C4b.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 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.
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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
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 195 citations in OpenAlex.
- Immunoglobulins with Non-Canonical Functions in Inflammatory and Autoimmune Disease States.International journal of molecular sciences · 2020Pooled it
- Serum IgM crosslinks hepatitis B subviral particles into supramolecular immune complexes.bioRxiv : the preprint server for biology · 2026Article
- Standardizing pre-existing anti-PEG antibody detection: A key to clarifying their binding features and clinical relevance.Journal of pharmaceutical analysis · 2026Article
- Immunoglobulin heavy chain locus duplication in bats.Science advances · 2026Article
- Reconstruction of the Flexible IgM Fc Core Using Atomic Force Microscopy Topography and the AFM-Assembly Pipeline.Journal of molecular recognition : JMR · 2026Article
- Engineering Liposomes and Polymer Conjugates: A Platform for Mechanistic Complement Activation Studies and Controlled Release Applications.ACS applied materials & interfaces · 2026Article
- Electroosmotic Flow-Driven Nanopore Translocation of Large, Conformationally Dynamic Proteins: Overcoming Steric and Electrostatic Barriers.Journal of the American Chemical Society · 2026Article
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- MtrE Loop2-specific multiple antigenic peptide vaccine and monoclonal antibody confer complement-dependent protection against Neisseria gonorrhoeae.NPJ vaccines · 2026Article
- The fc fragment of IgMs binds C1q to activate the first step of the classical complement pathway, while inhibiting complement-dependent cytotoxicity.The FEBS journal · 2026Article
- Neutralization of SARS-CoV-2 by IgM-14 via engagement of two distinct spike epitopes.PLoS pathogens · 2026Article
- The role of the complement system in gastrointestinal-related diseases.Frontiers in immunology · 2026Review
- Complement-mediated ADCP as a distinct and finite cytotoxic mechanism of monoclonal antibodies.Frontiers in immunology · 2026Article
- Pre-Existing Anti-Adeno-Associated Virus Immunity in Gene Therapy: Mechanisms, Challenges, and Potential Solutions.Human gene therapy · 2025Review
- Clinical and immunopathological spectrum of immunoglobulin M pemphigoid: a multicenter case series.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · 2025Article
- Review
- Article
- Therapeutic IgG- and IgM-specific proteases disarm the acetylcholine receptor autoantibodies that drive myasthenia gravis pathology.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Isotype conversion of Staphylococcal-specific IgG into IgM broadens the reactivity to other bacterial pathogens.Cell reports. Medicine · 2025Article
- Neutralizing Antibodies vs. Viruses: Interacting Mechanisms and Escape Tactics.Microorganisms · 2025Review
56 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
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antigen binding by serum Ig-M (IgM) protects against microbial infections and helps to prevent autoimmunity, but causes life-threatening diseases when mistargeted. How antigen-bound IgM activates complement-immune responses remains unclear. We present cryoelectron tomography structures of IgM, C1, and C4b complexes formed on antigen-bearing lipid membranes by normal human serum at 4 °C. The IgM-C1-C4b complexes revealed C4b product release as the temperature-limiting step in complement activation. Both IgM hexamers and pentamers adopted hexagonal, dome-shaped structures with Fab pairs, dimerized by hinge domains, bound to surface antigens that support a platform of Fc regions. C1 binds IgM through widely spread C1q-collagen helices, with C1r proteases pointing outward and C1s bending downward and interacting with surface-attached C4b, which further interacts with the adjacent IgM-Fab
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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.