ArticleProceedings of the National Academy of Sciences of the United States of America2011
Evasion of immunity to Plasmodium falciparum malaria by IgM masking of protective IgG epitopes in infected erythrocyte surface-exposed PfEMP1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 84 citations in OpenAlex.
- Induction of strain-transcending antibodies against Group A PfEMP1 surface antigens from virulent malaria parasites.PLoS pathogens · 2012Trial
- Vaccine-induced mouse antibodies targeting Plasmodium falciparum PfVFT antigen inhibit blood stages through multiple mechanisms.NPJ vaccines · 2026Article
- The grand escape - how pathogens outsmart the human complement system.Immunobiology · 2025Review
- A monoclonal antibody selectively recognizing PfEMP1 proteins associated with cerebral malaria.Scientific reports · 2025Article
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Borrelia burgdorferi Infection-Induced Persistent IgM Secretion Controls Bacteremia, but Not Bacterial Dissemination or Tissue Burden.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Cryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding of Plasmodium falciparum to Chondroitin Sulfate A.Nature communications · 2023Article
- Review
- Plasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M.Nature communications · 2023Article
- Review
- Factors influencing phagocytosis of malaria parasites: the story so far.Malaria journal · 2021Review
- Congenital Transmission of Apicomplexan Parasites: A Review.Frontiers in microbiology · 2021Review
- To React or Not to React: The Dilemma of Fish Immune Systems Facing Myxozoan Infections.Frontiers in immunology · 2021Review
- Binding of human serum proteins to Plasmodium falciparum-infected erythrocytes and its association with malaria clinical presentation.Malaria journal · 2020Article
- Rosettes integrity protects Plasmodium vivax of being phagocytized.Scientific reports · 2020Article
- VAR2CSA-Mediated Host Defense Evasion ofFrontiers in immunology · 2020Review
- Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it.Immunological reviews · 2020Review
- Comprehensive analysis of Fc-mediated IgM binding to the Plasmodium falciparum erythrocyte membrane protein 1 family in three parasite clones.Scientific reports · 2019Article
- Unravelling the cellular and molecular pathogenesis of bovine babesiosis: is the sky the limit?International journal for parasitology · 2019Review
- Molecular Principles of Intrauterine Growth Restriction in Plasmodium Falciparum Infection.Frontiers in endocrinology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Plasmodium falciparum malaria is a major cause of mortality and severe morbidity. Its virulence is related to the parasite's ability to evade host immunity through clonal antigenic variation and tissue-specific adhesion of infected erythrocytes (IEs). The P. falciparum erythrocyte membrane protein 1 (PfEMP1) family is central to both. Here, we present evidence of a P. falciparum evasion mechanism not previously documented: the masking of PfEMP1-specific IgG epitopes by nonspecific IgM. Nonspecific IgM binding to erythrocytes infected by parasites expressing the PfEMP1 protein VAR2CSA (involved in placental malaria pathogenesis and protective immunity) blocked subsequent specific binding of human monoclonal IgG to the Duffy binding-like (DBL) domains DBL3X and DBL5ε of this PfEMP1 variant. Strikingly, a VAR2CSA-specific monoclonal antibody that binds outside these domains and can inhibit IE adhesion to the specific VAR2CSA receptor chondroitin sulfate A was unaffected. Nonspecific IgM binding protected the parasites from FcγR-dependent phagocytosis of VAR2CSA(+) IEs, but it did not affect IE adhesion to chondroitin sulfate A or lead to C1q deposition on IEs. Taken together, our results indicate that the VAR2CSA affinity for nonspecific IgM has evolved to allow placenta-sequestering P. falciparum to evade acquired protective immunity without compromising VAR2CSA function or increasing IE susceptibility to complement-mediated lysis. Furthermore, functionally important PfEMP1 epitopes not prone to IgM masking are likely to be particularly important targets of acquired protective immunity to P. falciparum malaria.
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Registered trials
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