Non-O ABO blood group genotypes differ in their associations with Plasmodium falciparum rosetting and severe malaria

Abstract

Blood group O is associated with protection against severe malaria and reduced size and stability of P. falciparum-host red blood cell (RBC) rosettes compared to non-O blood groups. Whether the non-O blood groups encoded by the specific ABO genotypes AO, BO, AA, BB and AB differ in their associations with severe malaria and rosetting is unknown. The A and B antigens are host RBC receptors for rosetting, hence we hypothesized that the higher levels of A and/or B antigen on RBCs from AA, BB and AB genotypes compared to AO/BO genotypes could lead to larger rosettes, increased microvascular obstruction and higher risk of malaria pathology. We used a case-control study of Kenyan children and in vitro adhesion assays to test the hypothesis that double dose non-O genotypes (AA, BB, AB) are associated with increased risk of severe malaria and larger rosettes than single dose heterozygotes (AO, BO). In the case-control study, compared to OO, the double dose genotypes consistently had higher odds ratios (OR) for severe malaria than single dose genotypes, with AB (OR 1.93) and AO (OR 1.27) showing most marked difference (P=0.02, Wald test). In vitro experiments with blood group A-preferring P. falciparum parasites showed that significantly larger rosettes were formed with AA and AB host RBCs compared to OO, whereas AO genotype rosettes were indistinguishable from OO. Overall, the data show that ABO genotype influences P. falciparum rosetting and support the hypothesis that double dose non-O genotypes confer a greater risk of severe malaria than AO/BO heterozygosity.

Cerebral Malaria: Clinicians, Extracellular Vesicles, and Therapeutically-Rational Exchange (T-REX)

“…Here we try to use "clinician-friendly" terms and concepts. "Therapeutically-rational exchange transfusion" (T-REX) refers to different options [24][25][26][27][28][29][30] that may optimize "conventional" exchange-for-malaria in which special Pf-resistant donor RBCs are used instead of nondescript "standard-issue" blood-bank RBCs that might be Pf-promoting RBCs (like the adhesive, PfEMP1-binding group-A RBCs) [4,31,32]. Perhaps helpful visually: The pathogenic PfEMP1 proteins expressed by iRBCs can bind the blood-group A antigen expressed by type-A RBCs, and this binding promotes cytoadhesion (iRBC-uRBC interaction called "rosetting") that promotes microvascular blood flow obstruction.…”