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Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria
Michael F Duffy1, Rintis Noviyanti2, Takafumi Tsuboi3
1Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. mduffy@unimelb.edu.au.
Background:
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria.
Methods:
Parts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from laboratory isolates. Antibodies from Papuan patients to these parts of multiple PfEMP1 proteins were measured.
Results:
Patients with uncomplicated malaria were more likely to have antibodies that recognized PfEMP1 of Group C type and recognized a broader repertoire of group A and B PfEMP1s than patients with severe malaria.
Conclusion:
These data suggest that exposure to a broad range of group A and B PfEMP1s is associated with protection from severe disease in Papua, Indonesia.
Insights
Antibodies recognizing a wide variety of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants, particularly Group A and B types, are linked to protection against severe malaria in Papua, Indonesia.
Area of Science:
- Malariology
- Immunology
- Genetics
Background:
- Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants, encoded by var genes, are key mediators of malaria pathogenesis, including cytoadhesion and antigenic variation.
- PfEMP1s are classified into three main groups (A, B, C) and possess conserved domain structures known as domain cassettes.
- Evidence suggests a specific subset of PfEMP1s is associated with severe malaria, prompting investigation into antibody responses.
Purpose of the Study:
- To compare antibody reactivity against various PfEMP1 variants in patients with severe versus uncomplicated malaria.
- To determine if antibodies targeting specific PfEMP1 domains correlate with protection from or susceptibility to severe malaria.
Main Methods:
- RNA sequencing (RNAseq) was used to identify expressed var gene fragments in severe malaria patients.
- Several partial PfEMP1 domains were expressed, along with others from laboratory isolates.
- Antibody responses to these expressed PfEMP1 fragments were measured in Papuan patients.
Main Results:
- Patients with uncomplicated malaria exhibited a higher likelihood of possessing antibodies recognizing Group C PfEMP1 types.
- Uncomplicated malaria patients also showed broader antibody recognition of Group A and B PfEMP1 variants compared to severe malaria patients.
Conclusions:
- Exposure to a diverse range of Group A and B PfEMP1 variants appears to be associated with protection against severe malaria in the Indonesian Papua region.
- These findings highlight the potential role of broad antibody responses to PfEMP1 variants in malaria immunity.
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