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

description: <br> <b>Glycosidic exclusion*<sup>,</sup>** 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 type<sup>1</sup>, whom Charles Darwin would, by the history of his own family, the “<i>Darwin/Wedgewood Dynasty” </i><sup>2</sup><sup>, </sup><sup>3</sup>, 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<sup>4</sup><sup>,</sup> <sup>5</sup>. 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<sup>6</sup>. 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<sup>7</sup><sup>, </sup><sup>8</sup><sup>, </sup><sup>9</sup>, and core fucosylation of immunoglobulin heavy chains, in regulating assembly and intracellular signaling of precursor B cell receptors<sup>10</sup>, 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 fucosylation<sup>11</sup> while the rest of the seminal plasma demonstrates high levels of non-immunoglobulin-linked fucosyl residues<sup>12</sup>. 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<sup>13</sup> 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. & 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. Was the Darwin/Wedgwood Dynasty Adversely Affected by Consanguinity? <i>Bioscience</i>. 2010;60(5):376-383. doi:10.1525/bio.2010.60.5.7. 3. Álvarez G, Ceballos FC, Berra TM. Darwin was right : inbreeding depression on male fertility in the Darwin family. <i>Biol J Linn Soc</i>. 2014:1-10. doi:10.1111/bij.12433. 4. Watkins WM. Biochemistry and Genetics of the ABO, Lewis, and P blood group systems. <i>Adv Hum Genet</i>. 1980;10:1-136,379-385. 5. Kaneko, M., Nishihara, S., Shinya, N., Kudo, T., Iwasaki, H., Seno, T., Okubo, Y. & Narimatsu H. Wide variety of point mutations in the H gene of Bombay and para-Bombay individuals that inactivate H enzyme. <i>Blood</i>. 1997;90(2):839-849. 6. Dean L. Blood Groups and Red Cell Antigens. <i>ABO blood Gr</i>. 2005:Chapter 5. doi:10.1160/TH04-04-0251. 7. Masuda, K., Kubota, T., Kaneko, E., Iida, S., Wakitani, M., Kobayashi-Natsume, Y., Kubota, A., Shitara, K. & Nakamura K. Enhanced binding affinity for FcgammaRIIIa of fucose-negative antibody is sufficient to induce maximal antibody-dependent cellular cytotoxicity. <i>Mol Immunol</i>. 2007;44(12):3122-3131. http://www.sciencedirect.com/science/article/pii/S0161589007000776. 8. Iida, S., Kuni-Kamochi, R., Mori, K., Misaka, H., Inoue, M., Okazaki, A., Shitara, K. & Satoh M. Two mechanisms of the enhanced antibody-dependent cellular cytotoxicity (ADCC) efficacy of non-fucosylated therapeutic antibodies in human blood. <i>BMC Cancer</i>. 2009;9:58. doi:10.1186/1471-2407-9-58. 9. Yamane-Ohnuki N, Satoh M. Production of therapeutic antibodies with controlled fucosylation. <i>MAbs</i>. 2009;1(3):230-236. doi:10.4161/mabs.1.3.8328. 10. Li, W., Liu, Q., Pang, Y., Jin, J., Wang, H., Cao, H., Li, Z., Wang, X., Ma, B., Chi, Y., Wang, R., Kondo, A., Gu. J. & Taniguchi N. Core fucosylation of ?? heavy chains regulates assembly and intracellular signaling of precursor B cell receptors. <i>J Biol Chem</i>. 2012;287(4):2500-2508. doi:10.1074/jbc.M111.303123. 11. Kratz, E.M., Ferens-Sieczkowska, M., Faundez, & Kątnik-Prastowska I. Changes in fucosylation of human seminal IgG and secretory component of IgA in leukocytospermic patients. <i>Glycoconj J</i>. 2014;31(1):51-60. doi:10.1007/s10719-013-9501-y. 12. Olejnik, B., Kratz, E., Zimmer, M., & Ferens-Sieczkowska M. Glycoprotein fucosylation is increased in seminal plasma of subfertile men. <i>Asian J Androl</i>. 2015;17(2):274-280. doi:25248658. 13. Wang Y, Shao L, Shi S, et al. Modification of epidermal growth factor-like repeats with O-fucose: Molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase. <i>J Biol Chem</i>. 2001;276(43):40338-40345. doi:10.1074/jbc.M107849200. "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>