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

<br> <b>Glycosidic exclusion*^,** not protecting the “Oh” or <i>Bombay type. </i></b> <i><b> </b>Peter Arend</i> 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 <i>Bombay</i> blood type¹, whom Charles Darwin would, by the history of his own family, the “<i>Darwin/Wedgewood Dynasty” </i>²^,³, have analyzed to result from reduced fertility in consanguinities. The classical <i>Bombay type</i> 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 <i>Bombay</i> 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 encoded⁴^, 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 cytotoxicity⁷^,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 <i>Bombay type</i> individuals, the non-somatic glycosylation processes of embryogenic stem cell-to-germ cell transformation involving modification and <i>O</i>-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 References. 1. Bhende, Y. M., Deshpande, C. K., Bhatia, H. M., Sanger, Ruth., Race, R. R., Morgan W. T. &amp; Watkins WM. A “new” blood-group character related to the ABO system. 1952. <i>Natl Med J India</i>. 2008;21(5):3 p. doi:10.1016/S0140-6736(52)92356-8. 2. Berra TM, Alvarez G, Ceballos FC. 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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. <br> <br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br><br>