Study of Anti-BKPyV Immune Responses in Kidney Transplant Patients With BKPyV Viremia

Overview

The human pathogen BK polyomavirus (BKPyV) is a ubiquitous, small, non-enveloped DNA virus that infects over 90% of people, typically in childhood with mild or no symptoms. Following primary infection, BKPyV establishes latency predominantly in the reno-urinary tract, and can occasionally be detected in the urine without any concomitant clinical symptoms. However, among kidney transplant recipients (KTR), due to impaired cellular and humoral immunity, uncontrolled viral replication in renal tubular epithelial cells (RPTE) can occur, leading to high-level BKPyV DNAemia and significant damage to the reno-urinary system (ie polyomavirus-associated nephropathy). In the absence of any effective antiviral drug, the mainstay of therapy for significant BKPyV replication among KTR is reducing immunosuppressive drugs, despite the subsequent of risk of graft rejection. Current efforts to identify new monitoring and therapeutical strategies need to be supported by a better understanding of the dynamics of BKPyV-specific immune responses following transplantation. Although adaptive cellular and humoral immune responses play a crucial role in the control of BKPyV reactivation among healthy individuals, immunosuppression and transplantation disrupt immune homeostasis and reshape the immune response landscape both in terms of function and fitness to new stimuli. Consequently, pre-transplant prediction of patients who will be able to control post-transplant BKPyV reactivation or who will develop BKPyV-related complications remains challenging. This knowledge gap stems from insufficient studies on the comprehensive analysis of immune responses during BKPyV reactivation. In particular, most studies to date have not investigated the role of NK cells in this context, despite their potent antiviral activity, heterogenous repertoire in each patient and their recently uncovered adaptive properties. The hypothesis is that among KTR with de novo BKPyV DNAemia, the comprehensive analysis of anti-BKPyV immune responses (including both the description of NK cell repertoire and adaptive immune), could allow * A better stratification of KTR at-risk for BKPyV-related complications using accessible immune biomarkers. * The identification of the most efficient strategies of immunosuppression management for the control of BKPyV DNAemia, that could be further evaluated in a prospective cohort. * The identification of immunological correlates for the control of BKPyV DNAemia, which aim at providing a foundation for the development of future immunotherapeutic strategies.