Malaria tropica evades host immunity through ABO blood group hybridization

Coevolution of species drives diversity in animals and plants, while parasites that lack essential life functions compensate by exploiting the host cell machinery. In malaria tropica, the parasite <i>Plasmodium falciparum</i> does not encode the biologically indispensable amino sugar GalNAc (N-acetyl-d-galactosamine), and its serine molecules are linked to host GalNAc, catalysed by the blood group-independent polypeptide GalNAc transferase, which initiates infection. The resulting hybrid, developmental <i>O</i>-GalNAcα1-Ser/Thr-R, A-like/Tn ("T nouvelle") antigen represents the first step in pathogenesis, which in blood group A is completed by specific glycosylation encoded by the A allele, neutralising the pre-existing anti-A-like/Tn reactivity of polyreactive IgM and precluding A-phenotypic autoimmunity. In blood group O(H), this antibody blocks the formation of a hybrid A-like/Tn antigen, whereas in blood group A individuals, the duplication of host-pathogen exposure by two genetically distinct bindings and the neutralisation of anti-A-like/Tn IgM reactivity explain the increased susceptibility and severity of disease.