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Differential Plasmodium falciparum surface antigen expression among children with Malarial Retinopathy
Abdirahman I Abdi1,2, Symon M Kariuki1, Michelle K Muthui1
1KEMRI-Wellcome Trust Research Programme, P.O. Box 230-80108, Kilifi, Kenya.
Insights
Retinopathy in cerebral malaria patients does not correlate with DC8 or DC13 Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants. However, elevated Group A PfEMP1 expression in retinopathy suggests its role in cerebral malaria pathology.
Area of Science:
- Malariology
- Immunology
- Pathology
Background:
- Cerebral malaria is a severe complication of Plasmodium falciparum infection.
- Retinopathy serves as a clinical indicator for cerebral malaria, distinguishing parasite sequestration in the brain from other causes.
- Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates parasite sequestration in the brain via adherence to host receptors.
Purpose of the Study:
- To investigate the role of specific PfEMP1 variants (DC8 and DC13) in cerebral malaria with retinopathy.
- To determine if Group A PfEMP1 variants are associated with retinopathy in cerebral malaria patients.
Main Methods:
- Profiling PfEMP1 gene expression in Plasmodium falciparum parasites from children with cerebral malaria.
- Stratifying patients based on the presence or absence of retinopathy.
- Comparing the expression levels of DC8, DC13, and Group A PfEMP1 between retinopathy and non-retinopathy groups.
Main Results:
- No significant elevation of DC8 or DC13 PfEMP1 gene expression was found in children with retinopathy.
- A higher proportion of Group A PfEMP1 expression was observed in children with retinopathy compared to those without.
- This suggests Group A PfEMP1 variants may contribute to the pathology of cerebral malaria.
Conclusions:
- DC8 and DC13 PfEMP1 variants are unlikely to be the primary drivers of brain pathology in retinopathy-positive cerebral malaria.
- Group A PfEMP1 variants are associated with retinopathy in cerebral malaria and may be a target for therapeutic interventions.
- Targeting Group A PfEMP1 could potentially reduce brain pathology in severe malaria.
Abstract:
Retinopathy provides a window into the underlying pathology of life-threatening malarial coma ("cerebral malaria"), allowing differentiation between 1) coma caused by sequestration of Plasmodium falciparum-infected erythrocytes in the brain and 2) coma with other underlying causes. Parasite sequestration in the brain is mediated by PfEMP1; a diverse parasite antigen that is inserted into the surface of infected erythrocytes and adheres to various host receptors. PfEMP1 sub-groups called "DC8" and "DC13" have been proposed to cause brain pathology through interactions with endothelial protein C receptor. To test this we profiled PfEMP1 gene expression in parasites from children with clinically defined cerebral malaria, who either had or did not have accompanying retinopathy. We found no evidence for an elevation of DC8 or DC13 PfEMP1 expression in children with retinopathy. However, the proportional expression of a broad subgroup of PfEMP1 called "group A" was elevated in retinopathy patients suggesting that these variants may play a role in the pathology of cerebral malaria. Interventions targeting group A PfEMP1 may be effective at reducing brain pathology.
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