Explorative Insights into Local Immune Response to BK Virus—A Cross-Sectional Study in Urine Samples Between Transplant Recipients and Non-Immunocompromised Hosts

Background and Objectives: BK virus (BKPyV) is a common latent pathogen in humans, but it becomes particularly insidious in kidney transplant recipients, where reactivation may contribute to allograft loss. The immune mechanisms controlling BKPyV latency in immunocompromised hosts remain incompletely understood. We assume the urinary immune proteome reflects local immune response in the kidney and the urinary tract. Thus, this study aimed to determine whether the presence of BKPyV alters the urinary immune-related proteomic profile of kidney transplant recipients and shifts it away to that observed in healthy individuals. Materials and Methods: 137 urine samples were collected from kidney recipients, both BKPyV-positive and BKPyV-negative, patients with stage 5 chronic kidney disease, and healthy controls. Targeted proteomic analysis was performed using the proximity extension assay, followed by heatmapping, principal component analysis, random forest, and linear regression modeling. Results: The urinary proteome of BKPyV-positive recipients remained more distinct from healthy controls than that of BKPyV-negative ones. Among the 33 proteins detected across all samples, 17 showed significant intergroup differences, with KLRD1 (CD94) uniquely upregulated in all transplant recipients, but downregulated in BKPyV-positive samples. Conclusions: We conclude that the presence of BKPyV in the urinary tract of kidney recipients notably interplays with the local immune response even in the absence of clinical disease.