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

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.