Heart transplants are lifesaving for children with severe heart disease, but there are far too few donors worldwide. Hearts from donors with ABO blood groups mismatched to the recipient would allow access to an expanded pool, but this is generally not done because ABO antibodies would cause rapid damage and rejection. We showed that young children can safely receive ABO-mismatched transplants because they have immature immune systems and have not yet made ABO antibodies. This has resulted in more potential donors for children, changing the practice of infant heart transplantation globally.

Safe ABO-mismatched transplantation and effective care afterward require accurate detection of ABO antibodies. These are currently measured with the ‘hemagglutination’ test (red blood cell clumping) developed more than a century ago and has well-described flaws. Although this test works well for transfusion management, it is less helpful for transplant testing and decision-making for critically ill children. We developed a ‘slide-based’ test for ABO-antibodies and showed that this test precisely and predictably detects the presence, and importantly, confirms the absence, of ABO antibodies that would specifically react to the donor heart. Here, we propose to adapt our ABO antibody testing further to a ‘bead-based’ method, easier to use in clinical care and similar to testing already used commonly for HLA antibody assessment. Working internationally with HLA laboratories and centres performing heart transplants in children, we will use this new test to study how ABO antibodies are produced with age. Better characterization of ABO antibodies will increase the predictability and safety of ABO­mismatched heart transplantation, allowing consideration of expansion into older children and hard-to-match patients.

Aim 1: Validate our ABH bead-based assay to demonstrate that it can be performed in multiple clinical HLA laboratories with consistent and reproducible results.

Aim 2: Characterize normal childhood development of ABO antibodies specific to ASH-subtype antigens.

Aim 3: Investigate the role of genotype in influencing ABO antibody development.

We propose to study the development of both lgG and lgM isotype ASH-subtype-specific antibodies in healthy individuals and heart transplant patients across the age spectrum from infancy to adolescence using our newly developed ABO bead-based assay.