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Kidney Week

Abstract: TH-PO587

TCR NGS Based Evidence for Differential Diagnosis and Personalized Therapy in BKV Nephropathy

Session Information

  • Trainee Case Reports - II
    October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Reports

  • 1802 Transplantation: Clinical

Authors

  • Stervbo, Ulrik, University Hospital Marien Hospital Herne, Herne, Germany
  • Nienen, Mikalai, University Hospital Marien Hospital Herne, Herne, Germany
  • Viebahn, Richard, Ruhr University Bochum, Bochum, Germany
  • Westhoff, Timm H., University Hospital Marien Hospital Herne, Herne, Germany
  • Babel, Nina, University Hospital Marien Hospital Herne, Herne, Germany
Introduction

BKV nephropathy (BKVAN) is a disease in 10% of renal transplant recipients which might lead loss of the graft in up to 80% of the cases. Current the diagnosis is based on assessment of BKV viral load in serum with assessment of inclusion bodies by kidney biopsy for definitive diagnosis. In case of identified BKVAN, the principle treatment is to decrease or alter the immunosuppressive regimen. However, the pathological features of BKVAN overlap with those of acute cellular rejection, where decrease of immunosuppression is detrimental.

Case Description

We were presented with a German male, transplanted with a kidney from a close living relative. The patient had a high BKV load (432500 copies/ml), but histological findings demonstrated borderline rejection according to BANFF, and SV40 negative findings. Faced with the vexing question of increasing or decreasing immunosuppression we obtained blood and a biopsy from the patient. By way of magnetic bead enrichment of activated T-cells we isolated T-cells reactive to BKV and donor cells in a direct and indirect fashion. Together with the fresh renal tissue, the activated T-cells were prepared for next-generation sequencing (NGS) of the T-cell receptor (TCR). We isolated T-cells in all three activation modi, which indicates an expansion of virus as well as donor specific T-cells in the patient, and underpins the complexity of diagnosis. When we compared the TCR repertoires of activated peripheral T-cells to those in the biopsy, we observed a distinct and strong presence of BKV specific T-cells in the transplant. This clearly excluded acute cellular rejection and allowed confident decrease of the immunosuppressive regimen. The graft function improved and the patient shows no signs of BKV infection nor graft rejection.

Discussion

TCR NGS profiling is a novel, but labor insensitive technique. The turnaround time is about 5 days and donor derived cells are required for optimal results. Identification of the specificity of tissue infiltrating T-cells by TCR NGS is nonetheless a valuable technique for differential diagnosis and personalized therapy.