Korean J Transplant.  2023 Nov;37(Suppl 1):S265. 10.4285/ATW2023.F-8647.

Characterization of innate immune cell subtypes in kidney transplant recipients with BK virus infection through single-cell transcriptomic profiling of peripheral blood

• Bae H
• Ryu JH
• Lee J
• Ko GY
• Park Hs
• Cho SI
• Oh EJ

• KMID: 2551894
• DOI: http://doi.org/10.4285/ATW2023.F-8647

Abstract

Background
This study analyzed blood cell types in BK virus (BKV) infection among immunosuppressed kidney transplant recipients. It aimed to understand the single-cell transcriptional patterns of these subtypes in relation to BKV infection and its associated nephropathy, which poses a risk of graft loss.
Methods
We obtained peripheral blood mononuclear cells (PBMCs) from six kidney transplant recipients: one with stable graft function, two with detectable BKV (BK viremia), and three with BKV-associated nephropathy (BK nephropathy). Using the 10x Genomics Chromium Platform, we created single-cell libraries for each PBMC sample. Data were analyzed with the Cell-Ranger Pipeline and further explored using R programming and Seurat for downstream analysis.
Results
We conducted analysis on 5,473 stable, 9,068 BK viremia, and 17,238 BK nephropathy cells, unveiling 7,223 DEGs across 16 cell clusters. In BK nephropathy, gamma delta T cells stood out with 30.4% overexpression, emerging as the most distinct subtype among the 16 groups, compared with BK viremia and stable groups. Contrasting stable and BK viremia, FCGR3A monocytes overexpressed by 21.3% in stable group, featuring key genes like LYZ, FTL, CTSS, IFI30, FTH1. In gamma delta T cells, BK nephropathy exhibited elevated expression of genes including HIST1H4C, IL32, TMSB4X, CALM3, HMGB2 (log2FC diff=1.9–2.3). Similarly, within FCGR3A monocytes, stable group displayed elevated expression relative to BK nephropathy for genes like IFITM3, BCL2A1, CTSL, PHACTR1, WARS (log2FC diff=1.1–1.6). These findings emphasize gene expression disparities in BK viremia, nephropathy, and stable groups.
Conclusions
Reactivated BK virus can impact nephropathy progression through specific genomic interactions. Gamma delta T cells, with typically low expression in transplant recipients, elude conventional methods but are detected via single-cell RNA analysis. Similarly, FCGR3A monocytes show diverse gene overexpression among BK nephropathy, BK viremia, and stable groups. These markers could enhance post-kidney transplant patient management.