Single-cell profiling of peripheral immune remodeling in BK polyomavirus–associated nephropathy after kidney transplantation
4 affiliations
- 1Department of Medical Sciences, Graduate School of The Catholic University of Korea , ,
- 2Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, Bucheon St. Mary’s Hospital , ,
- 3Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea , ,
- 4Department of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea , ,
Abstract
BK polyomavirus–associated nephropathy (BKPyVAN) remains a major cause of allograft dysfunction after kidney transplantation. To define peripheral immune signatures associated with distinct clinical states of BKPyV infection, we performed single-cell RNA sequencing of peripheral blood mononuclear cells from kidney transplant recipients across three clinical states: stable graft function (n = 1), BKPyV DNAemia (n = 2), and biopsy-proven BKPyVAN (n = 3). We identified 17 immune cell populations and observed remodeling of both the innate and adaptive compartments. Monocyte subsets differed across clinical states, with CD16 ⁺ non-classical monocytes enriched in BKPyV DNAemia and inflammatory monocytes more abundant in BKPyVAN. CD8 ⁺ T-cell frequency was higher in BKPyVAN than in BKPyV DNAemia, while NK-cell frequency was lower in BKPyV DNAemia and BKPyVAN than in Stable, consistent with altered antiviral surveillance. A rare but transcriptionally distinct population, termed Activated Effector Cells (AECs), comprised only 0.60% of cells in BKPyVAN (104 of 17,238 cells) yet accounted for 12.15% of cluster-associated marker calls, the highest among the 17 populations, and displayed marked enrichment of cell cycle and RNA metabolic pathways. Across multiple lineages, AUC-based gene set enrichment analysis revealed convergent activation of RNA processing and intracellular transport pathways. Pseudobulk differential expression and permutation testing supported condition-associated transcriptional signatures, and leading-edge gene analysis identified candidate transcriptional readouts, including cell cycle regulators, inflammatory mediators, and RNA processing genes, with potential utility for blood-based monitoring. These findings reveal peripheral immune remodeling across the clinical states of BK polyomavirus infection and highlight the value of resolving rare, transcriptionally distinct immune populations, providing a rationale for noninvasive, transcriptomics-informed monitoring and risk stratification strategies.
Related
- Case Report: Late-onset BK polyomavirus-associated nephropathy with encephalitis, antibody-mediated rejection, and atypical hemolytic uremic syndrome: a rare overlap causing allograft dysfunction, therapeutic challenges, and multidisciplinary management
- Cronkhite-Canada Syndrome Associated with Primary Cutaneous Peripheral T-cell Lymphoma and Membranous Nephropathy: A Case Report
- Real-world use of extracorporeal photopheresis for BK polyomavirus infection after kidney transplantation: results from the French multicenter registry
- Axillary Dacron Graft Versus Direct Femoral Arterial Cannulation for Peripheral VA-ECMO After Heart Transplantation: A Single-Center Cohort Study
- Maximizing cardiopulmonary support as a minimally invasive platform—using peripheral parallel veno-venous and veno-arterial extracorporeal membrane oxygenation and axillary impella 5.5 as a bridge to heart–lung transplantation
BibTeX
@article{bae2026singlecell,
title = {{Single-cell profiling of peripheral immune remodeling in BK polyomavirus–associated nephropathy after kidney transplantation}},
author = {Hyunjoo Bae and Eun Jeong Ko and Byung Ha Chung and Eun-Jee Oh},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1939071},
url = {https://europepmc.org/article/PMC/PMC13668843},
note = {CC BY},
}
RIS
TY - JOUR
TI - Single-cell profiling of peripheral immune remodeling in BK polyomavirus–associated nephropathy after kidney transplantation
AU - Hyunjoo Bae
AU - Eun Jeong Ko
AU - Byung Ha Chung
AU - Eun-Jee Oh
PY - 2026
DA - 2026/10/01
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1939071
UR - https://europepmc.org/article/PMC/PMC13668843
AB - BK polyomavirus–associated nephropathy (BKPyVAN) remains a major cause of allograft dysfunction after kidney transplantation. To define peripheral immune signatures associated with distinct clinical states of BKPyV infection, we performed single-cell RNA sequencing of peripheral blood mononuclear cells from kidney transplant recipients across three clinical states: stable graft function (n = 1), BKPyV DNAemia (n = 2), and biopsy-proven BKPyVAN (n = 3). We identified 17 immune cell populations and observed remodeling of both the innate and adaptive compartments. Monocyte subsets differed across clinical states, with CD16 ⁺ non-classical monocytes enriched in BKPyV DNAemia and inflammatory monocytes more abundant in BKPyVAN. CD8 ⁺ T-cell frequency was higher in BKPyVAN than in BKPyV DNAemia, while NK-cell frequency was lower in BKPyV DNAemia and BKPyVAN than in Stable, consistent with altered antiviral surveillance. A rare but transcriptionally distinct population, termed Activated Effector Cells (AECs), comprised only 0.60% of cells in BKPyVAN (104 of 17,238 cells) yet accounted for 12.15% of cluster-associated marker calls, the highest among the 17 populations, and displayed marked enrichment of cell cycle and RNA metabolic pathways. Across multiple lineages, AUC-based gene set enrichment analysis revealed convergent activation of RNA processing and intracellular transport pathways. Pseudobulk differential expression and permutation testing supported condition-associated transcriptional signatures, and leading-edge gene analysis identified candidate transcriptional readouts, including cell cycle regulators, inflammatory mediators, and RNA processing genes, with potential utility for blood-based monitoring. These findings reveal peripheral immune remodeling across the clinical states of BK polyomavirus infection and highlight the value of resolving rare, transcriptionally distinct immune populations, providing a rationale for noninvasive, transcriptomics-informed monitoring and risk stratification strategies.
SN - 1664-3224
ER -