Metabolic signatures of T cells in BK virus-associated nephropathy (BKVAN): comparison of different immunosuppressive drugs and adaptation strategies

• Applicant: Lukas van de Sand
• Subject Area: Clinical Infectiology and Tropical Medicine
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 579308863

Allogeneic kidney transplantation is currently the most effective form of renal replacement therapy for chronic kidney disease (CKD), providing superior survival and quality of life compared to dialysis. However, even before transplantation, CKD patients display marked impairments in cellular and humoral immunity, leading to increased susceptibility to infections and reduced vaccine responses. After transplantation, the required immunosuppressive therapy further exacerbates immune dysfunction, increasing the risk of opportunistic infections and diminishing vaccine efficacy. One of the most clinically significant infectious complications is reactivation of BK polyomavirus (BKV). Following primary infection in childhood, BKV persists latently in the urinary tract. While typically harmless in immunocompetent hosts, it may reactivate under immunosuppression. Many patients initially develop asymptomatic viruria, which can progress to BK virus–associated nephropathy (BKVAN), threatening graft function and long-term survival. With no effective antiviral therapy available, management relies on reducing immunosuppression, which carries a risk of rejection. The molecular and immunological factors governing the switch from latency to active replication remain poorly understood, representing a critical knowledge gap. The proposed project addresses this unmet need by combining clinical observation with immunological and metabolic profiling to identify determinants of BKV reactivation and its impact on transplant outcomes. Part 1 will investigate BKV-specific T cells in patients with and without viremia using high-dimensional spectral flow cytometry and functional metabolic assays. The goal is to define the pathways and metabolic programs that enable effective viral control, thereby uncovering mechanisms of protective immunity. Part 2 will analyze the effects of immunosuppressive drugs on virus-specific T-cell function in vitro. BKV-specific T cells will be the primary focus, with CMV-specific T cells serving as controls. Cytokine production, metabolic activity, and proliferative capacity will be assessed under drug exposure. We hypothesize that distinct classes of immunosuppressive agents differentially impair virus-specific T-cell functions, producing characteristic patterns of reduced antiviral control. Together, both parts aim to advance understanding of the interplay between viral latency, host immunity, and therapeutic immunosuppression. The findings may guide individualized immunosuppressive strategies that reduce the risk of BKVAN while preserving essential immune protection. Ultimately, this work seeks to enable targeted risk stratification and early interventions to improve outcomes in kidney transplant recipients.

• DFG Programme: WBP Fellowship
• International Connection: Netherlands
• Host: Professor Ramon Arens, Ph.D.