<b>Malaria tropica - Blood group A hybridisation compensates for </b><b><i>Plasmodium falciparum’s</i></b><b> inability to synthesize the aminosugar N-acetylgalactosamine (GalNAc)</b>

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.