The protozoan eukaryotic parasite Plasmodium falciparum, pathogen of malaria tropica, does not survive outside its metazoan host assumingly due to an evolutionary incomplete protein glycosylation, lacking the synthesis of the amino sugar N-acetylgalactosamine (GalNAc) and glucosamine (Glc)-GalNAc epimerizations. Breaking the species barrier, the host's cellular machinery most likely performs metazoan trans-species O-GalNAc glycosylation, which in the human occurs predominantly in blood group A

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... atients and is performed on abundantly expressed serine residues, arising throughout the parasite's life-cycle. In blood group O(H) individuals, the resulting hybrid antigen formation comes under control of germline-encoded polyreactive non-immune immunoglobulin M (IgM), which in blood group A individuals has undergone the phenotypic glycosidic accommodation of plasma proteins and has lost the natural anti-A/Tn reactivity. In fact, apart from clonal selection of adaptive antibodies, phenotypic glycosylation molecularly excludes corresponding immunological reactions against the hybrid antigen in non-O blood groups, i.e., the germline-encoded IgM gets molecularly engaged in the formation of the hybrid antigen and becomes part of the adhesion process via the same metabolic step.