<b>Malaria tropica in blood group A compensates for </b><b><i>Plasmodium falciparum's</i></b><b> inability to synthezise the amino sugar N-acetyl-D-galactosamine (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 abundantly expresssed serine molecule becomes linked to host GalNAc, catalyzed by the blood group-independent polypeptide GalNAc transferase, which initiates infection. The resulting hybrid, developmental <i>O</i>-GalNAcα1-Ser/Thr-R, mucin-type 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, neutralizing 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 neutralization of anti-A-like/Tn IgM reactivity explain the increased susceptibility and severity of disease in this group.