ArticleJournal of immunology (Baltimore, Md. : 1950)2013
A novel domain cassette identifies Plasmodium falciparum PfEMP1 proteins binding ICAM-1 and is a target of cross-reactive, adhesion-inhibitory antibodies.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 2 of them syntheses that pooled it.
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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
85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- Meta-Analysis of Human Antibodies AgainstFrontiers in immunology · 2022Pooled it
- Meta-analysis of Plasmodium falciparummBio · 2019Pooled it
- Population genomics of virulence genes of Plasmodium falciparum in clinical isolates from Uganda.Scientific reports · 2017Trial
- CD36 recruits α₅β₁ integrin to promote cytoadherence of P. falciparum-infected erythrocytes.PLoS pathogens · 2013Trial
- VAR2CSA-reactive IgG in Brazilian women exposed toInfection and immunity · 2025Article
- A monoclonal antibody selectively recognizing PfEMP1 proteins associated with cerebral malaria.Scientific reports · 2025Article
- Var genes, strain hyperdiversity, and malaria transmission dynamics.Trends in parasitology · 2025Review
- Variable surface antigen expression, virulence, and persistent infection byMicrobiology and molecular biology reviews : MMBR · 2025Review
- The spatiotemporal transcriptional profiling of murine brain during cerebral malaria progression and after artemisinin treatment.Nature communications · 2025Article
- A paradoxical population structure of var DBLα types in Africa.PLoS pathogens · 2025Article
- A systems serology approach to identifying key antibody correlates of protection from cerebral malaria in Malawian children.BMC medicine · 2024Article
- Detection of naturally acquired, strain-transcending antibodies against rosettingInfection and immunity · 2024Article
- Review
- Natural immunity to malaria preferentially targets the endothelial protein C receptor-binding regions of PfEMP1s.mSphere · 2023Article
- Knobs, Adhesion, and Severe Falciparum Malaria.Tropical medicine and infectious disease · 2023Review
- 3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism.iScience · 2023Article
- CD36-A Host Receptor Necessary for Malaria Parasites to Establish and Maintain Infection.Microorganisms · 2022Review
- ICAM-1-binding Plasmodium falciparum erythrocyte membrane protein 1 variants elicits opsonic-phagocytosis IgG responses in Beninese children.Scientific reports · 2022Article
- Neutrophils impose strong immune pressure against PfEMP1 variants implicated in cerebral malaria.EMBO reports · 2022Article
- Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1.Infection and immunity · 2022Article
25 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
12 authors at 7 institutions in 4 countries.
Funding
Abstract
Cerebral Plasmodium falciparum malaria is characterized by adhesion of infected erythrocytes (IEs) to the cerebral microvasculature. This has been linked to parasites expressing the structurally related group A subset of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of IE adhesion ligands and to IEs with affinity for ICAM-1. However, recent evidence has cast doubt on both these associations, tempering hopes of the feasibility of developing a vaccine based on ICAM-1-binding PfEMP1. In this study, we report the identification of a domain cassette (DC) present in group A var genes from six genetically distinct P. falciparum parasites. The three domains in the cassette, which we call DC4, had a high level of sequence identity and cluster together phylogenetically. Erythrocytes infected by these parasites and selected in vitro for expression of DC4 adhered specifically to ICAM-1. The ICAM-1-binding capacity of DC4 was mapped to the C-terminal third of its Duffy-binding-like β3 domain. DC4 was the target of broadly cross-reactive and adhesion-inhibitory IgG Abs, and levels of DC4-specific and adhesion-inhibitory IgG increased with age among P. falciparum-exposed children. Our study challenges earlier conclusions that group A PfEMP1 proteins are not central to ICAM-1-specific IE adhesion and support the feasibility of developing a vaccine preventing cerebral malaria by inhibiting cerebral IE sequestration.
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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.