ArticleThe Journal of experimental medicine2014
Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
53 citing papers in PubMed, 85 citations in OpenAlex.
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- Emerging antimicrobial therapies for Gram-negative infections in human clinical use.npj antimicrobials and resistance · 2025Review
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- Agnostic B cell selection approach identifies antibodies against K. pneumoniae that synergistically drive complement activation.Nature communications · 2024Article
- Type 5 secretion system antigens as vaccines against Gram-negative bacterial infections.NPJ vaccines · 2024Review
- Antibody-Mediated Serum Resistance Protects Pseudomonas aeruginosa During Bloodstream Infections.The Journal of infectious diseases · 2024Article
- Re-visiting humoral constitutive antibacterial heterogeneity in bloodstream infections.The Lancet. Infectious diseases · 2024Review
- Host heterogeneity in humoral bactericidal activity can be complement independent.Frontiers in immunology · 2024Article
- Cloaking antibodies are prevalent inFrontiers in cellular and infection microbiology · 2024Article
- Influence of microbiota-driven natural antibodies on dengue transmission.Frontiers in immunology · 2024Article
- Hit 'em Where It Hurts: Gram-Negative Bacterial Lipopolysaccharide as a Vaccine Target.Microbiology and molecular biology reviews : MMBR · 2023Review
- Subversion of the Complement System by Pseudomonas aeruginosa.Journal of bacteriology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
Abstract
Although specific antibody induced by pathogens or vaccines is a key component of protection against infectious threats, some viruses, such as dengue, induce antibody that enhances the development of infection. In contrast, antibody-dependent enhancement of bacterial infection is largely unrecognized. Here, we demonstrate that in a significant portion of patients with bronchiectasis and Pseudomonas aeruginosa lung infection, antibody can protect the bacterium from complement-mediated killing. Strains that resist antibody-induced, complement-mediated killing produce lipopolysaccharide containing O-antigen. The inhibition of antibody-mediated killing is caused by excess production of O-antigen-specific IgG2 antibodies. Depletion of IgG2 to O-antigen restores the ability of sera to kill strains with long-chain O-antigen. Patients with impaired serum-mediated killing of P. aeruginosa by IgG2 have poorer respiratory function than infected patients who do not produce inhibitory antibody. We suggest that excessive binding of IgG2 to O-antigen shields the bacterium from other antibodies that can induce complement-mediated killing of bacteria. As there is significant sharing of O-antigen structure between different Gram-negative bacteria, this IgG2-mediated impairment of killing may operate in other Gram-negative infections. These findings have marked implications for our understanding of protection generated by natural infection and for the design of vaccines, which should avoid inducing such blocking antibodies.
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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.