HLA and non-HLA antibody profiling in the urine of kidney transplant recipients

Kidney transplantation is the preferred therapy for end-stage renal disease (ESRD), yet long-term graft survival remains limited. Effective preservation of transplanted kidneys is essential amid a persistent organ shortage. Post-transplant graft injury arises from both immune and nonimmune mechanisms. Advances in multi-omic technologies have increasingly unraveled pathways underlying graft rejection and tolerance. While most studies have centered on intragraft immune-cell infiltration and circulating biomarkers, the role of antibodies in acute rejection and other graft injuries is not fully studied. In this exploratory study, we employed a high-throughput antibody-profiling microarray to quantitatively assess IgG antibodies against Human Leukocyte Antigen (HLA) and non-HLA (nHLA) in urine samples from kidney transplant recipients experiencing graft injury, including acute rejection. We identified multiple HLA and nHLA antibodies that were selectively enriched in urine at the time of graft injury and acute rejection, indicating antigen-specific humoral responses detectable at the site of injury. This first-of-its-kind urinary antibody-profiling study reveals promising antibody signatures associated with graft injury. These findings support the potential development of noninvasive, personalized biomarkers for routine monitoring and earlier detection of rejection in kidney transplant recipients.