ArticleScientific reports2016
Stratification of responders towards eculizumab using a structural epitope mapping strategy.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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
15 citing papers in PubMed, 21 citations in OpenAlex.
- Mapping of C5-Blocking Monoclonal Antibodies Reveals New C5 Inhibitory Epitopes and Novel Modes of C5 Inhibition.Immunology · 2026Article
- In vivo evidence of effective complement modulation by TriFu in comparison to C5 inhibition and complement depletion.Blood advances · 2026Article
- Mapping of Antibody Structural Epitopes Using Bacterial Cell Surface Display of Folded Domains.Methods in molecular biology (Clifton, N.J.) · 2025Article
- An Overview of Epitopes and Methods for Antibody Epitope Mapping.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Cryo-electron microscopy reveals a single domain antibody with a unique binding epitope on fibroblast activation protein alpha.bioRxiv : the preprint server for biology · 2024Article
- Mammalian cell display with automated oligo design and library assembly allows for rapid residue level conformational epitope mapping.Communications biology · 2024Article
- Hydrogen Deuterium Exchange and other Mass Spectrometry-based Approaches for Epitope Mapping.Frontiers in analytical science · 2023Article
- Harnessing secretory pathway differences between HEK293 and CHO to rescue production of difficult to express proteins.Metabolic engineering · 2022Article
- Inflammation, immunity and potential target therapy of SARS-COV-2: A total scale analysis review.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2021Review
- Characterizing the original anti-C5 function-blocking antibody, BB5.1, for species specificity, mode of action and interactions with C5.Immunology · 2020Article
- Intact Transition Epitope Mapping - Targeted High-Energy Rupture of Extracted Epitopes (ITEM-THREE).Molecular & cellular proteomics : MCP · 2019Article
- Current and Future Approaches for Monitoring Responses to Anti-complement Therapeutics.Frontiers in immunology · 2019Review
- The rational design of affinity-attenuated OmCI for the purification of complement C5.The Journal of biological chemistry · 2018Article
- Staphylococcus carnosus: from starter culture to protein engineering platform.Applied microbiology and biotechnology · 2017Review
- Anti-complement component 5 antibody targeting MG4 domain inhibits choroidal neovascularization.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The complement component 5 (C5)-binding antibody eculizumab is used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical haemolytic uremic syndrome (aHUS). As recently reported there is a need for a precise classification of eculizumab responsive patients to allow for a safe and cost-effective treatment. To allow for such stratification, knowledge of the precise binding site of the drug on its target is crucial. Using a structural epitope mapping strategy based on bacterial surface display, flow cytometric sorting and validation via haemolytic activity testing, we identified six residues essential for binding of eculizumab to C5. This epitope co-localizes with the contact area recently identified by crystallography and includes positions in C5 mutated in non-responders. The identified epitope also includes residue W917, which is unique for human C5 and explains the observed lack of cross-reactivity for eculizumab with other primates. We could demonstrate that Ornithodorus moubata complement inhibitor (OmCI), in contrast to eculizumab, maintained anti-haemolytic function for mutations in any of the six epitope residues, thus representing a possible alternative treatment for patients non-responsive to eculizumab. The method for stratification of patients described here allows for precision medicine and should be applicable to several other diseases and therapeutics.
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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.