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

## TL;DR

This study explores how BK virus affects the immune response in kidney transplant recipients by analyzing urine samples and comparing them to non-immunocompromised individuals.

## Contribution

The study identifies specific immune proteins in urine that distinguish BKPyV-positive transplant recipients from healthy individuals.

## Key findings

- BKPyV-positive transplant recipients had a more distinct urinary proteome compared to healthy controls.
- KLRD1 (CD94) was uniquely upregulated in all transplant recipients but downregulated in BKPyV-positive samples.
- 17 out of 33 detected proteins showed significant differences between groups.

## Abstract

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.