Malaria tropica evades host immunity through ABO blood group hybridization

The coevolution of species drives diversity in animals and plants, while in host–parasite coevolution, a parasite may complete an incomplete function by utilizing the host cell’s machinery. <i>Plasmodium falciparum</i> (P. falciparum), the pathogen of malaria tropica, does not encode the amino sugar N-acetyl-d-galactosamine (GalNAc) and therefore cannot synthesize the immediate, developmental blood group- independent, (serologically A-like) <i>O</i>-GalNAcα1-Ser/Thr-R, Tn ("T nouvelle") antigen. If the parasite compensates for this deficiency by hijacking the human GalNAc metabolism and attaching it to serine molecules, expressed throughout its life cycle, the resulting hybrid A-like/Tn antigen is completed by A-allelic glycosylation in blood group A and represents the first step in the pathogenesis of malaria tropica. In blood group O(H), this formation is blocked by the natural anti-A/Tn-reactive, poly-reactive immunoglobulin M (IgM), which in blood group A is neutralized by A-allelic glycosylation, explaining the increased susceptibility and severity of disease in blood group A individuals.<br><br><br><br><br><br><br><br><br>