Abstract: SA-PO381
Clinical Characteristics and T-Cell Exhaustion in BK Polyomavirus Infection After Pediatric Kidney Transplantation
Session Information
- Pediatric Nephrology - III
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Author
- Lin, Ching-Yuang, Children's Hospital, China Medical University, Taiwan, Taichung, Taiwan
Background
BK virus (BKV) is a significant cause of chronic kidney injury in kidney transplant recipients that results in allograft loss. Inhibitory receptors PD-1 and Tim-3 play a crucial role in regulating CD8 T cell function during chronic infection. The study's aim 1 was to determine the clinical characteristics of those who had BK viremia versus those who did not. Aim 2 was to document correlation between exhausted PD-1 and Tim-3 exhausted T cells during chronic BKV infection.
Methods
The retrospective case-control study was conducted from January 2008 to July 2022. The subjects were composed of a total of 32 pediatric KTRs and 12 with BKV viremia, in which 5 of 12 had BKVN were obtained. Peripheral blood mononuclear cells (PBMCs) were collected during episodes of BKV viremia. PD-1, Tim-3, and CD8 T cells were evaluated by multiparameter flow cytometry.
Results
BKV viremia was observed in 12/32 (37.5%) and BKVN in 5/32 (15.6%). Induction therapy was not significantly different between BKV and non-BKV viremia groups. The mean time for BK detection was 4.1 months after renal transplantation. Percent rise in serum creatinine correlated with intensity of viral load. The first-line therapy after identification of BKV viremia was a decreased dosage in Tacrolimus (100%) and intravenous immunoglobulin, and discontinuing mycophenolate mofetil. When reduction in immunosuppressant was not sufficient to decrease viral load, 4/12 (33.3%) of patients received leflunomide. High expression of PD1 and Tim-3 on CD8 cells with more severe T cells exhaustion was noted during chronic BKV infection. The treatment resistance was also accompanied with persistent high level of PD-1 and Tim-3 expression on CD8 T cells. There was no difference in the percentage of graft survival between BKV viremia and non-BKV viremia after 8 years' follow-up.
Conclusion
Patients with the highest viral loads and longest duration of BKV viremia are at risk of BKVN. Expression of PD-1, Tim-3 and CD8 T cell indicates chronic T cell partial exhaustion. BKV viremia and CD8 T cell exhaustion may be a surrogate marker for adjusting immunosuppressant reduction and intravenous immunoglobulin treatment.