„Glycosidic exclusion“ not protecting the „Oh“ or Bombay Type

Glycosidic exclusion*^,** not protecting the “Oh” or Bombay type.

 Peter Arend

The molecular biological relationship between human fertility and the ABO(H) blood group phenotype formation becomes visible through special cell surface structures and immunoglobulin M specificities arising in people with the rare Oh or Bombay blood type¹, whom Charles Darwin would, by the history of his own family, the “Darwin/Wedgewood Dynasty” ^{2, 3}, have analyzed to result from reduced fertility in consanguinities. The classical Bombay type is characterized by the lack of expression of any ABO(H) epitope and instead shows the development of high isoagglutinin levels, additionally exerting strong binding of complement to anti-H agglutinin. The red cell surface presents with the naked structure Gal-β1-R, which has not been completed for the H-receptor (Fuc-α1-2-Gal-β1-R), thereby representing the structural fundament for ABOH epitopes. In its native form, the Bombay type occurs in individuals with the extremely rare genotype (h/h;se/se). This molecular biological phenomenon is explained by point mutations at the H- and Se genes on chromosome 19 such that the fucosyltransferases FUT1 and FUT2 are not encoded^{4, 5}. FUT1 and FUT2 are epistatically connected with the A and B allelic glycotransferase functions encoded on chromosome 9, and fucosyl residues provide the functional-structural basis of the formation of any ABOH phenotype on the cell surface or in secretions and plasma proteins⁶. Moreover, immunoglobulins are heavily fucosylated and fucosyl residues appear, through developmental varying of the positions between the cell surfaces and the heavy chains of immunoglobulins to augment or reduce antibody-mediated cellular cytotoxicity^{7, 8, 9}, and core fucosylation of immunoglobulin heavy chains, in regulating assembly and intracellular signaling of precursor B cell receptors¹⁰, most likely represents a key mechanism of clonal selection. In fact, the seminal IgG of leucocytospermic infertile men appears to be characterized by poor core fucosylation¹¹ while the rest of the seminal plasma demonstrates high levels of non-immunoglobulin-linked fucosyl residues¹². Thus, in Bombay type individuals, the non-somatic glycosylation processes of embryogenic stem cell-to-germ cell transformation involving modification and O-fucosylation of EGF¹³ are most likely exposed to metabolic competition with multiple glycosidic sites of poorly fucosylated, glycan-depleted immunoglobulins.

*Arend, Peter: ABO phenotype and innate isoagglutinin specificities as they arise from “glycosidic exclusion” and relate to human reproduction. A hypothesis 

 https://dx.doi.org/10.6084/m9.figshare.1368271.

**Arend, Peter: Human fertility and ABO(H) histo (blood) group completenes as they relate to somatic fucosylations,  https://dx.doi.org/10.6084/m9.figshare.2007132

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"Glycosidic exclusion" (figure) is primarily based on somatic fucosylation: In cases, in which a protective superiority of the human A- (and/or B) allele over OH appears to exist, such superiority is likely exerted exclusively in epistatic functional connection with the H and/or Se genes and non-specifically augments the glycosidic protection by additional carbohydrate.