Role of ABO Secretor Status in Mucosal Innate Immunity and H. pylori Infection

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Abstract
The fucosylated ABH antigens, which constitute the molecular basis for the ABO blood group system, are also expressed in salivary secretions and gastrointestinal epithelia in individuals of positive secretor status; however, the biological function of the ABO blood group system is unknown. Gastric mucosa biopsies of 41 Rhesus monkeys originating from Southern Asia were analyzed by immunohistochemistry. A majority of these animals were found to be of blood group B and weak-secretor phenotype (i.e., expressing both Lewis a and Lewis b antigens), which are also common in South Asian human populations. A selected group of ten monkeys was inoculated with Helicobacter pylori and studied for changes in gastric mucosal glycosylation during a 10-month period. We observed a loss in mucosal fucosylation and concurrent induction and time-dependent dynamics in gastric mucosal sialylation (carbohydrate marker of inflammation), which affect H. pylori adhesion targets and thus modulate host–bacterial interactions. Of particular relevance, gastric mucosal density of H. pylori, gastritis, and sialylation were all higher in secretor individuals compared to weak-secretors, the latter being apparently “protected.” These results demonstrate that the secretor status plays an intrinsic role in resistance to H. pylori infection and suggest that the fucosylated secretor ABH antigens constitute interactive members of the human and primate mucosal innate immune system. The common ABO blood group antigen system was described in the early 20th century. In addition, it has been known for 60 years that the majority of individuals also express the corresponding ABO antigens (carbohydrate identity tags) in their saliva, tears, milk, and mucus secretions in the digestive tract. To this date, however, the biological function of the ABO blood group antigens has remained an enigma. Here, we show that the great majority of Rhesus monkeys are of blood group B and weak-secretors, i.e., are similar to the human populations in South Asia from where these monkeys originate. This observation suggests that an evolutionary adaptation in digestive tract mucosal carbohydrate patterns to local environmental selection has occurred. In addition, we demonstrate that long-term infection by the “peptic ulcer bacterium” Helicobacter pylori induces mucosal carbohydrate patterns that change according to the individual secretor phenotype. The common weak-secretor monkeys were apparently “protected,” as they had stable glycosylation, lower inflammation, and lower bacterial infection load, whereas the less common secretor animals had increased levels of inflammation-associated mucosal carbohydrate patterns and a transient decrease in the ABO blood group system type of carbohydrates. These novel observations suggest that the individual ABO blood group and secretor phenotype are part of human and non-human primate innate immunity against infectious disease.