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Plasmodium falciparum malaria and the immunogenetics of ABO, HLA, and CD36 (platelet glycoprotein IV)


Christine M. Cserti-Gazdewich, MD, FRCPC, Departments of Medicine, Hematology, and Laboratory Hematology, Blood Transfusion Medicine Laboratory, University Health Network/Toronto General Hospital, 3EC-306, 200 Elizabeth Street, Toronto, ON M5G-2C4, Canada


Plasmodium falciparum malaria has long been a killer of the young, and has selected for polymorphisms affecting not only erythrocytes, but the immunogenetics of three histocompatibility systems: ABO, human leukocyte antigen (HLA), and CD36. The ABO system is important because the original allele, encoding glycosylation with the A sugar, acts as an adhesion ligand with infected red blood cells (iRBC), thereby promoting vasoocclusion. The prevalence of blood group O, which reduces this cytoadhesion, has increased in endemic areas. Other adaptations which could mitigate A-mediated rosetting include weaker A expression and increased soluble A secretion. The role of the HLA system in malaria has been harder to verify. Although HLA-B53 and DRB1*04 may be associated with clinical outcome, HLA studies are challenged by numerous comparisons in this most polymorphic of systems, and confounded by increasingly heterogeneous populations. Certain HLA markers may also reflect linkage artefact with other malaria-relevant polymorphisms. HLA may be less important because the parasite predominantly invades a compartment which does not express HLA. Adhesion of iRBCs is also mediated by CD36, expressed on platelets, monocytes, and microvascular endothelium. CD36 on monocytes is involved in clearing iRBC, while CD36 on platelets and the endothelium may play a role in tissue sequestration. The genetics of CD36 expression are complex, and recent research is fraught with inconsistent results. The solution may lie in examining genotype–phenotype correlations, zygosity effects on differential tissue expression, or other mechanisms altering CD36 tissue expression. Carefully designed prospective studies should bridge the gap between in-vitro observations and clinical outcomes.