Funding outcome

ABO blood group structures are sugars (A, B or O) on red blood cells and organs. Expression of these sugars determines our blood type. We naturally produce antibodies to the sugars that are not our own. For example, blood type O people, who express neither A or B sugars, have antibodies to A and B sugars. For blood transfusions and for transplants the presence of these antibodies means we normally need to match blood types. However, if ABO-mismatched transplantation could be safely performed it would increase the number of transplants and save lives. ABO antibodies do not begin to develop until about 6 months of age. Dr. West was the first to show that ABO-mismatched transplantation could safely be performed in infants because they lack these antibodies. Dr. West also showed as children grow, they don't produce ABO antibodies to the mismatched heart, a process called immune tolerance. Our proposed project will lead to new knowledge about the development of ABO antibody. We will use an exciting new method we developed to monitor antibodies in blood that recognize ABO sugars. This test will give us new information about the types of antibodies that recognize ABO sugars. As some studies are difficult or impossible to do in humans, for our initial studies we will use a mouse model. We will study the role of sex and age in natural ABO antibody development, as well as the impact of the gut microbiome (microorganisms in the gut) and 'T cells' (known to help B cells make antibody). Our findings to-date show that ABO antibodies are produced at much higher amounts in female vs. male mice. We will investigate this interesting sex difference in detail. Having a better understanding of how ABO antibodies develop may allow for ABO-mismatched heart transplantation to be extended safely beyond infancy. This would have the potential to improve the well-being of the many older children awaiting heart transplantation.