BK Polyomavirus-Specific 9mer CD8 T Cell Responses Correlate With Clearance of BK Viremia in Kidney Transplant Recipients: First Report From the Swiss Transplant Cohort Study

Abstract

BK polyomavirus (BKPyV) causes premature kidney transplant (KT) failure in 1-15% of patients. Because antivirals are lacking, most programs screen for BKPyV-viremia and, if positive, reduce immunosuppression. To evaluate the relationship of viremia and BKPyV-specific immunity, we examined prospectively cryopreserved plasma and peripheral blood mononuclear cells at the time of transplantation (T0) and at 6 mo (T6) and 12 mo (T12) after transplant from 28 viremic KT patients and 68 nonviremic controls matched for the transplantation period. BKPyV IgG seroprevalence was comparable between cases (89.3%) and controls (91.2%; p = 0.8635), but cases had lower antibody levels (p = 0.022) at T0. Antibody levels increased at T6 and T12 but were not correlated with viremia clearance. BKPyV-specific T cell responses to pools of overlapping 15mers (15mer peptide pool [15mP]) or immunodominant CD8 9mers (9mer peptide pool [9mP]) from the early viral gene region were not different between cases and controls at T0; however, clearance of viremia was associated with stronger 9mP responses at T6 (p = 0.042) and T12 (p = 0.048), whereas 15mP responses were not informative (T6 p = 0.359; T12 p = 0.856). BKPyV-specific T cells could be expanded in vitro from all patients after transplant, permitting identification of 78 immunodominant 9mer epitopes including 50 new ones across different HLA class I. Thus, 9mP-responses may be a novel marker of reconstituting CD8 T cell function that warrants further study as a complement of plasma BKPyV loads for guiding immunosuppression reduction.

Impact of donor BK polyomavirus replication on recipient infections in living donor transplantation

“…In a pediatric cohort, Ali et al found that a recipient's low anti‐BKPyV titer was associated with an increased risk of early BKPyV infection at post‐transplantation, particularly in the context of a donor with a high anti‐BKPyV titer. In the present study, we found that 91% of recipients were seropositive for BKPyV similar to other studies . Herein, we did not observe any relationship between recipients’ sero‐reactivity at transplantation and post‐transplant BKPyV replication.…”

“…BKPyV titer. In the present study, we found that 91% of recipients were seropositive for BKPyV similar to other studies 26,41. Herein, we did not observe any relationship between recipients' sero-reactivity at transplantation and post-transplant BKPyV replication.…”

JC polyomavirus‐specific antibody responses in pediatric kidney transplant recipients

“…recent case-control study of the Swiss transplant cohort study reported a significant increase only in BKPyV-specific IgG activity in BKPyV-DNAemic patients, whereas their JCPyV-IgG activities remained unchanged 26. This emphasizes the potential relevance of the JCPyV-IgG responses seen in this pediatric study, since technical differences could be ruled due to the use of the same normalized VLP-based ELISA in the same laboratory.…”

“…Several case reports describe manifestations of JC‐PyVAN after KT, but most were detected in adults, in whom the seroprevalence is high and the risk of significant JCPyV exposure would be presumably lower or mitigated . In support of this notion, a recent case‐control study of the Swiss transplant cohort study reported a significant increase only in BKPyV‐specific IgG activity in BKPyV‐DNAemic patients, whereas their JCPyV‐IgG activities remained unchanged . This emphasizes the potential relevance of the JCPyV‐IgG responses seen in this pediatric study, since technical differences could be ruled due to the use of the same normalized VLP‐based ELISA in the same laboratory.…”

Donor‐derived, metastatic urothelial cancer after kidney transplantation associated with a potentially oncogenic BK polyomavirus

“…Importantly, all stages of the UC in our patient were LTag‐positive, suggesting that expression of this virus‐encoded transforming function contributed to malignant progression. The now relapse‐free time of 4 years after diagnosis of this metastasizing UC also points to the role of regaining anti‐tumour immunity following cessation of immunosuppression, and questions the need for additional aggressive therapeutic interventions in such situations .…”