Eric Koonming Ho, DHA

My research has focused on the immunologic mechanisms of allosensitization and its clinical consequences in heart, lung, and kidney transplantation. Through a series of studies spanning both adult and pediatric populations, my colleagues and I elucidated the pivotal role of donor-specific alloantibodies in influencing cardiac allograft survival. Our early work established that the presence of anti-HLA antibodies—whether pre-transplantation or de novo, formed post-transplant—correlates strongly with adverse outcomes, caused by antibody-mediated rejection and chronic allograft vasculopathy. By employing solid-phase assays, we demonstrated that de novo alloantibody production after transplantation is a dominant predictor of late graft loss, underscoring the dynamic nature of post-transplant sensitization.

In pediatric heart recipients, we identified unique patterns of alloantibody development distinct from adults, reflecting both age-related immune responses and differences in immunosuppressive exposure. These findings helped refine risk-stratification strategies and informed monitoring protocols for younger patients. Complementing this work, we investigated the relationship between solid-phase antibody detection and classical complement-dependent cytotoxicity crossmatching in renal transplantation, revealing that sensitive assays can identify clinically significant antibodies that are missed by traditional techniques. This contribution supported the broader adoption of solid-phase platforms in clinical histocompatibility testing.

Some of my research focused on the cellular mechanisms of rejection and tolerance. We discovered that chronic allograft rejection is primarily caused by the indirect allorecognition pathway, which results in intermolecular and intramolecular spreading of allo-epitopes from dominant and restricted to one haplotype to cryptic and presented on both HLA haplotypes of the host. We further identified a new population of allospecific T suppressor cells that have the CD8+CD28- phenotype and act in a contact-dependent, cytokine-independent manner due to the overexpression of transcriptional repressor BCL6, which inhibits the production of IL2, interferon gamma, and granzyme B. In a further attempt to study our transplant population, we developed a new method to monitor their immune response to COVID-19, utilizing a new approach that involves HLA tetramers coated with viral peptides and loaded onto microbeads phagocytosed by T cells with viral-specific TCRs.

Building on this foundation, my current research integrates artificial intelligence and machine-learning approaches to model the complex interplay among donor-specific antibodies, donor-derived cell-free DNA, and molecular markers of rejection. By combining immunogenetic, serologic, and clinical datasets, these computational frameworks aim to identify predictive biomarkers of antibody-mediated injury and improve patient-specific risk forecasting. This emerging field of AI-driven transplant immunology has the potential to transform precision monitoring and enable individualized immunosuppression strategies, thereby extending long-term graft survival.