Transcriptomic and histological analyses reveal immune dysregulation in BK virus-associated nephropathy

Abstract BK virus-associated nephropathy (BKVN) is an important cause of kidney allograft failure and involves complex immune responses. This study aimed to characterize gene expression changes and immune microenvironment features in BKVN tissues using transcriptomic analysis. Using the public dataset GSE47199, we performed differential expression, functional enrichment, and immune infiltration analyses on renal biopsy samples from patients with BKVN (n = 3) and transplant controls (n = 14), followed by immunohistochemistry (IHC) and immunofluorescence (IF) validation. We identified 2,838 differentially expressed genes (DEGs) between the groups. Functional enrichment analysis showed significant enrichment of immune- and inflammation-related terms, including “leukocyte proliferation,” “regulation of T cell activation,” and the “NF-kappa B signaling pathway.” Immune checkpoint molecules (CD274/PD-L1, CTLA4, TIGIT), pro-inflammatory factors (IFNG, IL6), and interferon-induced genes (MX1, IFIT2) were significantly upregulated in BKVN tissues (P < 0.05), whereas IRF3 showed an upward trend. CIBERSORT analysis indicated decreased relative proportions of CD8⁺ T cells and regulatory T cells (Tregs). In contrast, IHC showed increased PD-L1 but reduced IRF3 protein expression, while IF demonstrated marked CD8⁺ T-cell infiltration with increased PD-1 expression and partial spatial overlap with CD8.Overall, BKVN was characterized by broad immune activation and inflammatory responses. The discrepancy between reduced relative CD8⁺ T-cell proportions and increased local infiltration may reflect the complexity of the BKVN immune microenvironment. Increased immune checkpoint expression may suggest T-cell exhaustion or local immunosuppression, providing further insight into immune-mediated allograft injury associated with BKV infection and supporting further investigation of local immune dysregulation in BKVN.