ABH blood group and Lewis antigens are not only found on red blood cells, where A and B determine the group, but these molecules are also present in a wide variety of tissues and can trigger susceptibility to infections and contribute to the development of other thromboembolic and cardiovascular diseases.
Secretor status and ABH antigens (FUT2 gene)
The epithelia of the gastrointestinal, respiratory, urinary and reproductive tracts express lipid-conjugated carbohydrates (glycolipids) and proteins (glycoproteins) on their surfaces that include the ABH and Lewis antigens. These antigens confer essential biological properties, participate in intercellular turnover and trafficking, and are involved in cellular interaction during development.
The FUT2 gene codes for an enzyme, known as α-1,2-fucosyltransferase, which is essential for the secretion of the soluble forms of the ABH and Lewis blood group antigens into the mucosa and secretory glands. Such soluble antigens produce significant physiological changes in the tissue microenvironment, affecting bacterial adherence and immunoglobulin status, among other processes.
Polymorphisms that decrease α-1,2-fucosyltransferase enzyme activity such as W143X in Caucasians and I129F in Asians, produce the "non-secretory" phenotype characterized by not having these antigens in body secretions and, consequently, affect their susceptibility to many pathogens and diseases.
Stowell CP, Stowell SR. Biologic roles of the ABH and Lewis histo-blood group antigens Part I: infection and immunity. Vox Sang. 2019;114(5):426-442.
Stowell SR, Stowell CP. Biologic roles of the ABH and Lewis histo-blood group antigens part II: thrombosis, cardiovascular disease and metabolism. Vox Sang. 2019 Aug;114(6):535-552.
Velkova A, Diaz JEL, Pangilinan F, Molloy AM, Mills JL, Shane B, Sanchez E, et al. The FUT2 secretor variant p.Trp154Ter influences serum vitamin B12 concentration via holo-haptocorrin, but not holo-transcobalamin, and is associated with haptocorrin glycosylation. Hum Mol Genet. 2017;26(24):4975-4988.
Azad MB, Wade KH, Timpson NJ. FUT2 secretor genotype and susceptibility to infections and chronic conditions in the ALSPAC cohort. Version 2. Wellcome Open Res. 2018.