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Updated: Apr 7, 2026
Measuring Naturally Acquired Phagocytosis-Inducing Antibodies to Plasmodium falciparum Parasites by a Flow Cytometry-Based Assay
Published on: August 6, 2020
Immunoglobulin response to Plasmodium falciparum RESA proteins in uncomplicated and severe malaria
Cyril Badaut1, Léa Guyonnet2,3,4, Jacqueline Milet5,6
1Equipe résidente de recherche en infectiologie tropicale, Institut de Recherche Biomédicale des Armées (IRBA), Brétigny sur Orge, France. cbadaut@gmail.com.
Background:
The three members of the ring-infected erythrocyte surface antigen (RESA) proteins family share high sequence homologies, which impair the detection and assignment to one or another protein of some pathogenic processes inherent to Plasmodium falciparum malaria. The present study was intended to determine if the antibody and inflammatory responses of children living in a malaria-endemic area varied depending on the RESA-1, RESA-2 or RESA-3 proteins and the severity of the disease, two groups of severe and uncomplicated malaria cases being considered.
Methods:
Two synthetic peptides representing predicted B cell epitopes were designed per RESA protein, all located outside of the 3' and 5' repetition blocks, in order to allow an antibody detection specific of each member of the family. Recombinant rRESA-1B and rRESA-3B proteins were also engineered. Two groups of Beninese children admitted to hospital in 2009 for either uncomplicated or severe malaria were compared for their plasma levels of IgG specifically recognizing each recombinant RESA protein or synthetic peptide, and for their plasma inflammatory cytokine levels (IFN-γ, TNF-α and IL-10), taking into account host and parasite genetic factors.
Results:
The absence of IgG cross-reactivity between rRESA proteins and their protein carrier as well as between each RESA peptide and a non-epitopic RESA control peptide validated the use of the engineered recombinant proteins and peptides for the measurement of plasma IgG. Taking into account age, fever duration and parasitaemia, a multiple logistic regression performed on children clustered according to their antibody responses' profiles concluded to an increased risk of severe malaria for P2 (representative of RESA-1) responders (P = 0.007). Increased IL-10 plasma levels were found in children harbouring multiclonal P. falciparum infections on the basis of the T1526G resa2 gene polymorphism (P = 0.004).
Conclusions:
This study provided novel tools to dissect the seroreactivity against the three members of the RESA protein family and to describe its relation to protection against malaria. It suggested the measurement of plasma antibodies raised against specific peptides to serve as predictive immunologic markers for disease severity. Lastly, it reinforced previous observations linking the T1526G resa2 gene mutation to severe malaria.
Insights
Antibody responses to Plasmodium falciparum ring-infected erythrocyte surface antigen-1 (RESA-1) proteins indicate an increased risk of severe malaria. Specific RESA protein antibodies may predict disease severity, and a RESA2 gene mutation is linked to severe malaria.
Area of Science:
- Immunology
- Malariology
- Genetics
Background:
- The ring-infected erythrocyte surface antigen (RESA) protein family in Plasmodium falciparum shares high homology, complicating the study of pathogenic processes.
- Understanding differential immune responses to RESA-1, RESA-2, and RESA-3 is crucial for diagnosing and managing malaria severity.
Purpose of the Study:
- To investigate variations in antibody and inflammatory responses to RESA-1, RESA-2, and RESA-3 proteins in children with severe versus uncomplicated malaria.
- To identify potential serological markers for predicting malaria disease severity.
Main Methods:
- Developed specific synthetic peptides and recombinant proteins for each RESA family member to enable precise antibody detection.
- Assessed plasma IgG levels against RESA proteins/peptides and inflammatory cytokine profiles (IFN-γ, TNF-α, IL-10) in Beninese children with severe or uncomplicated malaria.
- Analyzed host and parasite genetic factors, including the T1526G resa2 gene polymorphism.
Main Results:
- Validated the specificity of engineered recombinant proteins and peptides, confirming no cross-reactivity.
- Identified an increased risk of severe malaria associated with antibody responses to RESA-1 (P2 responders) (P = 0.007).
- Observed elevated IL-10 levels in children with multiclonal P. falciparum infections linked to the T1526G resa2 gene polymorphism (P = 0.004).
Conclusions:
- Novel tools were developed to differentiate serological responses to the RESA protein family, aiding in understanding malaria protection.
- Plasma antibodies against specific RESA peptides show promise as predictive markers for malaria disease severity.
- Reinforced the association between the T1526G resa2 gene mutation and severe malaria cases.
