Kidney transplantation is life saving and compared to dialysis improves patient quality of life and decreases healthcare costs over time, but graft longevity is compromised by immunologic rejection and inadequate immunosuppression. Furthermore, the response to treatment for T-cell mediated rejection (TCMR) can be variable, is currently not predictable by clinical diagnostics nor understood from a mechanistic sense, and even partial treatment failure is associated with shortened graft longevity.
Intra-graft mechanisms of TCMR are poorly defined, largely because canonical methods of studying T cell biology require quantities of tissue that are not feasible to obtain longitudinally, T cells in dense extracellular matrix of the kidney are difficult to extract, and relevant animal models are poorly replicative of chronic disease in humans. Nevertheless, vast numbers of archived longitudinal allograft biopsy samples, with fine-grained contemporaneous clinical data, exist in the medical record and pathology archives. Therefore, there is both a strong need to develop novel approaches to interrogate residual diagnostic biopsy samples, and a unique opportunity to gain knowledge from materials and data already at hand, to improve patient outcomes in kidney transplantation and to further understand the behavior of T cells in human tissues.
Toward this, we are developing purpose-built discovery-based assays designed for maximal efficiency of information return from residual small biopsy allograft samples taken in the clinical course of kidney transplantation and held in pathology archives.