Transfusion-induces donor-specific antibody boost leading to antibody-mediated rejection after heart transplantation:...

Despite significant advances in immunosuppression strategies, antibody-mediated rejection (AMR) remains a leading cause of graft dysfunction and loss after heart transplantation. Donor-specific anti-HLA antibodies (DSA), either preformed or de novo, are key contributors. Blood transfusion is a frequent sensitizing event that can amplify alloimmune responses. We report the case of a 64-year-old woman transplanted for end-stage ischemic cardiomyopathy, requiring ECMO support, who developed severe AMR shortly after receiving red blood cell and pooled platelet transfusions. Although pre-transplant DSA were weakly detectable, a massive immunization boost occurred within days, leading to high levels of preformed DSA (detected in serum and biopsy eluate). Notably, analysis of antibodies eluted directly from the graft biopsy confirmed the presence of tissue-bound class I and II DSA, providing direct evidence of their pathogenic involvement, despite a negative retrospective Complement Dependent Cytotoxicity (CDC) crossmatch. Histological examination confirmed AMR (C4d+, pAMR2). Intensive therapy with corticosteroids, plasmapheresis and IVIg allowed partial control. This case highlights the importance of post-transfusion monitoring of anti-HLA antibodies to detect early alloimmunization and guide immunosuppressive strategies to reduce AMR.