Malaria tropica evades host immunity through ABO blood group hybridization

The coevolution of species drives diversity in animals and
plants and contributes to natural selection, while in host–parasite
coevolution, a parasite may complete an incomplete evolutionary/developmental
function by utilizing the host cell’s machinery. Analysis of related older data suggests that <i>Plasmodium falciparum</i> (<i>P.
falciparum</i>), the pathogen of malaria tropica, cannot survive outside its human
host because it is unable to
perform the evolutionarily first protein
glycosylation or blood group-independent (serologically A-like) <i>O</i>-GalNAcα1-Ser/Thr-R,
Tn antigen (“T nouvelle”) formation owing to its inability for synthesizing the amino sugar <i>N</i>-acetyl-d-galactosamine
(GalNAc). This parasite breaks the species
barrier via hijacking the host's A-like/Tn formation by abundantly expressing
serine residues and creating hybrid A-like/Tn structures.
In the human blood group O(H), these
hybrid structures are attacked by the
germline-encoded nonimmune polyreactive immunoglobulin M (IgM), which
physiologically regulates the expression of the syngeneic A-like/Tn
antigen. In non-O blood groups, this antibody molecule has undergone the
phenotypic accommodation of plasma proteins, which
results in loss of blood group A- and B-corresponding anti-A and anti-B isoagglutinin activities. This loss allows
the generation of human A- and B allele-connected hybrid epitopes and the
development of life-threatening disease
almost exclusively in non-O blood groups. Although malaria infection occurs
regardless of the blood group, the synthesis of the blood group AB enables the
strongest contact with the pathogen, and molecularly precluding any
isoagglutinin activity makes this group the least protected and the smallest
among the ABO blood groups. In contrast, blood group O(H) individuals have the
least contact with the pathogen; they maintain the isoagglutinins, rarely develop
severe disease, and survive this coevolution in an immunological balance with
the pathogen as the largest blood group worldwide.