부산대학교 도서관

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 and BO genotypes 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. Author summary: The most common human blood group, ABO, affects susceptibility to multiple diseases including malaria, whereby the non-O blood groups A, B and AB are associated with an increased risk of severe malaria in comparison to blood group O. This may occur because red blood cell (RBC) surface-expressed non-O blood group antigens mediate binding to P. falciparum-infected RBCs to form clumps known as rosettes, that occlude microvasculature circulation and cause severe malaria pathology. Nevertheless, to date, these conclusions have largely been based on ABO blood groups determined by serological antibody typing. Genetic classification into AO, AA, BO, BB, AB and OO offers a finer and more specific classification of ABO blood groups, but associations with severe malaria and rosetting based on this method have not been described previously. In a case-control study of >5000 Kenyan children, we show that the "double dose" non-O genotypes AA, BB and AB are associated with an increased risk to severe malaria compared to the "single dose" non-O genotypes AO and BO, and that this is most significant for AB versus AO. In in vitro experiments, double dose non-O genotypes formed larger rosettes compared to single dose non-O genotypes, providing a potential explanation for their increased severe malaria risk. [ABSTRACT FROM AUTHOR]