Ulrik Stervbo, Germany has been granted the Challenging Cases Competition Awards
BKV nephropathy (BKVAN) is a serious complication after renal transplantation (RTx) leading to a graft loss in up to 50% of affected patients. The diagnosis is based on assessment of BKV viral load in serum and histological findings in transplant biopsy. The presentation of BKVAN might mimic acute rejection, but the therapeutic approaches are completely contrary. Thus, specific tools for precise differential diagnosis are required for kidney transplant patients with BKV reactivation and unclear graft function deterioration. Here, we present a case of personalized therapy for renal graft function deterioration based on analysis of transplant infiltrated T-cells in a living-related RTx patient with sustained severe BKV-reactivation (VL> 400000copies/mL) and histological findings of acute rejection BANFF IIa. Due to the known difficulties with differential diagnosis, we applied our new technology identifying specificity of tissue infiltrating T-cells. In details, T-cell receptor (TCR) sequences of the graft infiltrated T-cells were analyzed by means of next generation sequencing in T-cells obtained from the graft biopsy. The TCRs of the biopsy were compared to BKV-specific and allograft-specific TCRs in peripheral blood. We found a strong presence of BKV specific T-cells in the transplant. While 12.95% of infiltrated cells had BKV-specificity, allograft-specificity was almost neglectable (1.22%). The following immunomodulating therapy led to the sustained resolution of BKV reactivation and significant improvement of allograft function (creatinine decrease from 4mg/dL to 2.7mg/dL) within 2 months. Thus, the identification of the specificity of tissue infiltrating T-cells by TCR NGS is a valuable technique which enables differential diagnosis and personalized therapy.
