ABO phenotype protected reproduction as it is based on specific fucosylations

Peter Arend
2016 Figshare  
The molecular biological relations between the formation of the ABO(H) blood group phenotype and human fertility is evident in the rare (Oh) or Bombay blood type, which Charles Darwin would have interpreted as resulting from reduced fertility in consanguinities, based on the history of his own family, the Darwin/Wedgewood Dynasty. In its native form, the Bombay type occurs in individuals with an extremely rare genotype (h/h; se/se), which does not produce the fucosyltransferases FUT1and FUT2
more » ... ses FUT1and FUT2 encoded on chromosome 19 due to point mutations. In fact, the Bombay type individual cannot synthesize the fucosyl residues or H- receptor, which in epistatic connection with the A- and B-allelic glycotransferases, encoded on chromosome 9, provides the structural basis for the formation of ABO(H) phenotypes on the cell surfaces, secretions and plasma proteins, such as van Willebrand factor (vWF), clotting factor VIII and the α2-macroglobulin (A2M) The innate isoagglutinins instead show extremely high levels of a mercaptoethanol-sensitive, complement-binding anti-H reactivity, acting over a wide range of temperatures, with an amplitude at 370C. This reactivity appears to be dominated by immunoglobulin M (IgM), which in view of the role of immunoglobulin fucosylation and the induction of antibody-mediated cytotoxicity (ADCC) by defucosylated immunoglobulin G (IgG), hypothetically promotes anti-self-reactive ADCC, that although not exerted by normal IgM, may be exerted by defucosylated IgM. Alternatively, the unusual temperature amplitude of the anti-H-reactive IgM, characteristic for Bombay type plasma, highly suggests the involvement of IgG. Moreover, most examples of IgM apparently have a significant IgG component. While the anti-H reactivity of the Bombay type plasma thus indicates the functions of several immunoglobulin classes, the defucosylation of at least the IgM should be genetically identical with that of the cell surfaces, and thus also results from the lack [...]
doi:10.6084/m9.figshare.1409398.v381 fatcat:ad56vr5hjrbmpafhnqpk63b35y