Cytokine Gene Polymorphisms Modulate Isohemagglutinin Titers and Classes: Another Aspect Towards the Link Between ABO Groups and Human Pathologies?

Anti-A and anti-B antibodies are essential for monitoring adverse reactions in organ transplants and transfusions. However, their importance is also growing due to their involvement in the pathophysiology of various human diseases, such as infections, although this is currently the subject of heated debate. A characteristic heterogeneity in the titers and classes of anti-A and anti-B antibodies is observed among individuals. Several factors appear to be responsible, such as everyone’s specific immune profile, age, sex, microbiota composition, lifestyle, and health status. The immune profile, the result of a specific genetic predisposition and mediated and controlled by cytokines, shows a bidirectional relationship with ABO antigen expression, the gut microbiota, and the levels and class switching of anti-ABO antibodies. Associations between ABO groups and circulating levels of cytokines and chemokines further highlight this complex interaction. To better understand the role of the immune profile in this context, we evaluated, for the first time, the possible association between polymorphic variants in the regulatory regions of the genes encoding the cytokines IL-8, IL-1, IL-4, IL-6, IFN-γ, and IL-10 and anti-A and anti-B antibody titers and classes by group and in total. We also assessed the levels of these cytokines in each group and their correlations with anti-A and anti-B antibodies, as well as with age and associations with gender. Significant data were obtained that may contribute to a better understanding of the other roles of ABO antibody titers.