Cellular immune response during BK polyomavirus infection in living donor kidney transplant recipients.

Abstract

Background: BK polyomavirus (BKPyV) is a significant cause of graft impairment and loss following kidney transplantation. Early prediction of which patients are at risk of BKPyV replication and BKPyV-associated nephropathy (BKPyVAN) would be beneficial, preferably prior to transplantation. From an immunological perspective, determinants of susceptibility to BKPyV reactivation remain incompletely understood. The aim of this study was to evaluate the prognostic value of lymphocyte subset counts, CD4/8 T cell ratio, and changes in CD4 + T cell counts over time. Additionally, the concept of Immune Risk Profile (IRP), defined as CD4/CD8 ratio combined with cytomegalovirus (CMV) seropositivity, was evaluated as an immunological tool to estimate the risk of developing a clinically significant BKPyV replication.

Methods: This study was part of a single-centre prospective cohort including adult kidney transplant recipients between 2016 and 2018 at Uppsala University Hospital, Sweden. All recipients were routinely screened for BKPyV DNA in plasma and urine every 3 months for up to 18 months after transplantation. Immune cell phenotyping was performed using flow cytometry on blood samples collected from both living donors and recipients at the time of transplantation, as well as from recipients during follow-up.

Results: In 21 of the 68 recipients (31%), BKPyV replication was detected in blood and/or urine; 11 (16%) had DNAemia. Recipients who later developed BKPyV replication had lower CD4/CD8 ratios before transplantation compared to those who remained BKPyV replication negative. Seventeen recipients (25%) met the criteria for IRP-positivity, of whom 9 (53%) developed BKPyV replication, indicating a higher risk compared to the IRP-negative recipients (OR 3.66, 95% CI 1.08-10.79; p = 0.034). The total T cell counts, as well as CD4 + and CD8 + T cell counts, increased 1-2 months post-transplantation compared with pre-transplant levels in both recipients who developed BKPyV replication and those who did not.

Conclusions: Recipients with a low CD4/CD8 ratio and IRP-positive status were more likely to develop subsequent BKPyV replication, supporting a role for T cell imbalance in susceptibility to viral reactivation. However, the observed differences were modest and substantial overlap between the groups limits the clinical utility of these markers for individualizing BKPyV.