ArticleInfection and immunity2015
Toxin-mediated paracellular transport of antitoxin antibodies facilitates protection against Clostridium difficile infection.
Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
- A time-to-event analysis of the exposure-response relationship for bezlotoxumab concentrations and CDI recurrence.Journal of pharmacokinetics and pharmacodynamics · 2020Trial
- Article
- Fc-FcγR interactions during infections: From neutralizing antibodies to antibody-dependent enhancement.Immunological reviews · 2024Review
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
- Stool Interleukin-1β Differentiates Clostridioides difficile Infection (CDI) From Asymptomatic Carriage and Non-CDI Diarrhea.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- The Murine Neonatal Fc Receptor Is Required for Transport of Immunization-Induced C. difficile-Specific IgG to the Gut and Protection against Disease but Does Not Affect Disease Susceptibility.Infection and immunity · 2021Article
- Immune response againstTherapeutic advances in gastroenterology · 2021Review
- Host Immune Responses toFrontiers in microbiology · 2021Review
- A probiotic yeast-based immunotherapy againstScience translational medicine · 2020Article
- Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies.Infectious diseases and therapy · 2020Review
- A Novel, Orally Delivered Antibody Therapy and Its Potential to PreventFrontiers in microbiology · 2020Article
- Synthetic Oligosaccharide-Based Vaccines Protect Mice fromACS chemical biology · 2019Article
- Clostridium difficile toxins induce VEGF-A and vascular permeability to promote disease pathogenesis.Nature microbiology · 2019Article
- Bezlotoxumab for the prevention ofInfection and drug resistance · 2019Review
- Host-targeted niclosamide inhibits C. difficile virulence and prevents disease in mice without disrupting the gut microbiota.Nature communications · 2018Article
- Overview of Antibody Drug Delivery.Pharmaceutics · 2018Review
- Treatment of Clostridium difficile Infection with a Small-Molecule Inhibitor of Toxin UDP-Glucose Hydrolysis Activity.Antimicrobial agents and chemotherapy · 2018Article
- Bezlotoxumab: an emerging monoclonal antibody therapy for prevention of recurrentBiologics : targets & therapy · 2018Review
- Review
- Epitopes and Mechanism of Action of the Clostridium difficile Toxin A-Neutralizing Antibody Actoxumab.Journal of molecular biology · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The exotoxins TcdA and TcdB are the major virulence factors of Clostridium difficile. Circulating neutralizing antitoxin antibodies are protective in C. difficile infection (CDI), as demonstrated, in part, by the protective effects of actoxumab and bezlotoxumab, which bind to and neutralize TcdA and TcdB, respectively. The question of how systemic IgG antibodies neutralize toxins in the gut lumen remains unresolved, although it has been suggested that the Fc receptor FcRn may be involved in active antibody transport across the gut epithelium. In this study, we demonstrated that genetic ablation of FcRn and excess irrelevant human IgG have no impact on actoxumab-bezlotoxumab-mediated protection in murine and hamster models of CDI, suggesting that Fc-dependent transport of antibodies across the gut wall is not required for efficacy. Tissue distribution studies in hamsters suggest, rather, that the transport of antibodies depends on toxin-induced damage to the gut lining. In an in vitro two-dimensional culture system that mimics the architecture of the intestinal mucosal epithelium, toxins on the apical side of epithelial cell monolayers are neutralized by basolateral antibodies, and antibody transport across the cell layer is dramatically increased upon addition of toxin to the apical side. Similar data were obtained with F(ab')2 fragments, which lack an Fc domain, consistent with FcRn-independent paracellular, rather than transcellular, transport of antibodies. Kinetic studies show that initial damage caused by apical toxin is required for efficient neutralization by basolateral antibodies. These data may represent a general mechanism of humoral response-mediated protection against enteric pathogens.
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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.