Central immunological position of the human blood group O in light of the Duffy groups
Blood group A phenotype development is associated with the impaired formation of adaptive and innate immunoglobulins due to clonal selection and phenotypic, glycosidic accommodation of the plasma proteins. This group is significantly burdened with an increased risk of developing distinct types of cancer when compared with the blood group O and is exerting strong susceptibility to Malaria tropica or infection by Plasmodium falciparum. While Malaria tertiana, caused by Plasmodium vivax, ovale and
... um vivax, ovale and knowlesi, is the best documented type of malaria, P. falciparum causes the most severe disease. In both malaria types, the risk of developing the disease is, although with reverse outcomes, molecularly strongly related to blood group phenotype formation; while the Duffy positive (Fya) individuals are most susceptible to P. vivax infections but the Duffy antigen receptor for chemokines (DARC) protein exerts cancer regulation, the human blood group A shows significant susceptibility to both life-threatening infection by P. falciparum and distinct types of cancer. Aside from the molecular features of the DARC protein, the phenotype-determining glycotransferase(s) from blood group A, affecting the levels of anti-A/Tn cross-reactive immuno-globulins, may also initiate the entry of Plasmodium merozoites into the host's red blood cells (RBCs) via the parasite's serine repeat antigen (SERA), which when exposed to cancerous O-GalNAc "A-like" (Tn) glycosylation, may provide the invasion of the parasite into a cancer cell as well. In contrast, the human blood group O is currently discussed to have a survival advantage of the overall risk of developing cancer; moreover, it rarely develops life-threatening malaria disease and offers the widest functional flexibility in adaptive and germline-encoded innate immunity.