Central immunological position of the human blood group O and phenotype-determining enzymes in growth and infectious disease

Peter Arend
2017 Figshare  
Development of the blood group A phenotype is associated with the impaired formation of adaptive and innate immunoglobulins due to clonal selection and phenotypic, glycosidic accommodation of plasma proteins. Compared with individuals from blood group O(H), individuals with blood group A have a significantly higher risk of developing certain types of cancer and exhibit strong susceptibility to malaria tropica or infection by Plasmodium falciparum. Although malaria tertiana, caused by Plasmodium
more » ... aused by Plasmodium vivax, is the best-documented type of malaria, P. falciparum causes the most severe disease. In both malaria types, the risk of developing disease is molecularly strongly related to blood group phenotype formation, although outcomes are reverse; while the Duffy positive (Fya) individuals are most susceptible to P. vivax infections but the Duffy antigen receptor for chemokines (DARC) protein exerts marked cancer regulation, 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 immunoglobulins, might also explain the adhesion of the parasite to host cells via the parasite's serine repeat antigen (SERA), which when exposed to cancerous GalNAcα1-O-Ser/Thr-R, "A-like" (Tn) glycosylation, suggests to provide 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, it rarely develops life-threatening malaria disease and offers the widest functional flexibility in adaptive and germline-encoded innate immunity.
doi:10.6084/m9.figshare.4714618.v228 fatcat:ht32mar4bvexjojwt5mquyr4ay