Central immunological position of the human histo (blood) group O(H)

Peter Arend
2017 Figshare  
Prokaryotic "blood group A/B-like" antigenic structures basically induce cross-reactive anti-A/B immunoglobulins, which due to clonal selection neither arise in blood group A nor in B individuals but occur exclusively in blood group O. While bacterial endotoxins non-specifically stimulate the formation of all immunoglobulins, involving the anti-A/B isoagglutinins, a definite, adaptive immunological induction of these agglutinins appears to be restricted to blood group O(H) individuals. In the
more » ... dividuals. In the non-O blood groups, anti-A/B reactivity is exerted by a primarily blood group-independent, polyreactive and thymus-independent non-immune IgM molecule that has undergone the phenotype-specific, glycosidic accommodation of plasma proteins, which reduces or excludes anti-self reactivity, however, necessarily involves impairment of immunity. While blood group A phenotype development thus is associated with impaired formation of adaptive and innate immunoglobulins, it promotes susceptibility to malaria infection via its intrinsic enzyme functions, initiating a self-destructive glycosidic, phenotypic accommodation of a "wrong eukaryote". Blood group A phenotype-specific GalNAc transferase activities, expressed by both cell surfaces and plasma proteins, and serine/threonine kinases from Plasmodium falciparum, which over the parasite's life cycle get into the red blood cell (RBC) of the human host, might provide the metabolic condition for adhesion protein and RBC rosette formation, assumingly based on heterologous O-glycosylation, breaking a species barrier and completing the "serine repeat antigen". Thus, the lack of blood group A phenotype-specific GalNAc glycosylation(s) most likely explains the obvious protection of human blood group O(H) individuals from severe malaria infection, and suggests a new molecular definition of the immunological (therapeutic) target. In fact, the human histo (blood) group O finally represents the worldwide most common blood type, associated with a superior, complex immunity, [...]
doi:10.6084/m9.figshare.4714618.v135 fatcat:fkvxuxv4hjbf7e6x5rsy5a2bya