DOI: 10.6084/m9.figshare.2067387.v29
title: „Glycosidic exclusion“ not protecting the „Oh“ or Bombay Type

description: "Glycosidic exclusion" not protecting the "Oh" or Bombay Type <b> </b>Peter Arend<b> *,**.</b> 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 type (1), 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 encoded. 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 proteins. 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 (4; 5; 6). In fact, the seminal IgG of leucocytospermic infertile men appears to be characterized by poor core fucosylation (7), while the rest of the seminal plasma demonstrates high levels of non-immunoglobulin-linked fucosyl residues (8; 9; 10). 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 EGF (11) 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.) Y.M. Bhende, C.K. Deshpande, H.M. Bhatia, R. Sanger, R.R. Race, W.T. Morgan, & W. M.Watkins, A “new” blood-group character related to the ABO system. 1952., Natl. Med. J. India. 21 (2008) 3 p. doi:10.1016/S0140-6736(52)92356-8. 2.) T.M. Berra, G. Alvarez & F.C. Ceballos, Was the Darwin/Wedgwood Dynasty Adversely Affected by Consanguinity?, Bioscience. 60 (2010) 376–383. doi:10.1525/bio.2010.60.5.7. 3.) G. Álvarez, F.C. Ceballos &T.M. Berra, Darwin was right : inbreeding depression on male fertility in the Darwin family, Biol. J. Linn. Soc. (2014) 1–10. doi:10.1111/bij.12433. 4.) K. Masuda, K., Kubota, T., Kaneko, E., Iida, S., Wakitani, M., Kobayashi-Natsume, Y., Kubota, A., Shitara, K. & Nakamura, Enhanced binding affinity for FcgammaRIIIa of fucose-negative antibody is sufficient to induce maximal antibody-dependent cellular cytotoxicity.Mol.Immunol.44(2007)3122–31. http://www.sciencedirect.com/science/article/pii/S0161589007000776. 5.) M. Iida, S., Kuni-Kamochi, R., Mori, K., Misaka, H., Inoue, M., Okazaki, A., Shitara, K. & Satoh, Two mechanisms of the enhanced antibody-dependent cellular cytotoxicity (ADCC) efficacy of non-fucosylated therapeutic antibodies in human blood., BMC Cancer. 9 (2009) 58. doi:10.1186/1471-2407-9-58. 6.) N. Yamane-Ohnuki & M. Satoh, Production of therapeutic antibodies with controlled fucosylation., MAbs. 1 (2009) 230–6. doi:10.4161/mabs.1.3.8328. 7.) E.M. Kratz, M. Ferens-Sieczkowska, R. Faundez, & I. Kątnik-Prastowska, Changes in fucosylation of human seminal IgG and secretory component of IgA in leukocytospermic patients, Glycoconj. J. 31 (2014) 51–60. doi:10.1007/s10719-013-9501-y. 8.) G.C. Domino, S.E. Hurd, E.A. Thomsson, K.A. Karnak, D.M. Holmen Larsson, J.M. Thomsson, E. Bäckström, M., & Hansson, Cervical mucins carry alpha(1,2)fucosylated glycans that partly protect from experimental vaginal candidiasis., Glycoconj. J. 26 (2009) 1125–34. doi:10.1007/s10719-009-9234-0. 9.) J. Smith, P. Myers, J. Rogers, C., Zhou, L. Petryniak, B. Becker, D. Homeister, & J. Lowe, Conditional control of selectin ligand expression and global fucosylation events in mice with a targeted mutation at the FX locus., J. Cell Biol. 158 (2002) 801–15. doi:10.1083/jcb.200203125. 10.) B. Olejnik, E.M. Kratz & M. Zimmer, Glycoprotein fucosylation is increased in seminal plasma of subfertile men., Asian J Androl. 17 (2015) 274–80. doi:2524865. 11.) Y. Wang, L. Shao, S. Shi, R.J. Harris, M.W. Spellman, P. Stanley, et al., Modification of epidermal growth factor-like repeats with O-fucose: Molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase, J. Biol. Chem. 276 (2001) 40338–40345. doi:10.1074/jbc.M107849200. Abbreviations: ESC = embryonic stem cells; EGF= epidermal growth factor.GC = germ cells. <br> <br> <br> <br>