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

Abstract

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.

Influence of host factors and parasite biomass on the severity of imported Plasmodium falciparum malaria

“…Persistence of protection after leaving malaria-endemic areas has already been suggested, but few biological data on immune responses are available [29, 30]. However, the differences in clinical presentation, observed in second-generation migrants and travelers/expatriates suggest the possibility that other factors are involved in protection against SM [31, 32]. Moreover, the difference in antibody response between first-generation migrants and second-generation migrants may also result from differences in exposure to the parasite.…”

Clinical Role of Human Leukocyte Antigen in Health and Disease

“…Despite their intracellular development, remarkable immune evasion is achieved. The erythrocyte is arguably appealing not only for its nutritive iron and protein content, but also for its lack of continued HLA expression after enucleation [51], thereby unable to process and present immunologic signature units for adaptive immune recognition [52].…”

Evolutionary aspects of ABO blood group in humans

“…It has recently been suggested that this severe infection may have played an important role in driving the current ABO distribution among populations in endemic areas [15][16][17][18][19][20][21][22][23]. In a recent review, Cserti and Dzik critically analyzed the literature on the association between the ABO system and P. falciparum malaria, showing that group O subjects tend to exhibit a favorable outcome than group A individuals [18]. In their experimental studies, Fry and colleagues [22] and Rowe and colleagues [21] provided a biological explanation for this clinical finding.…”