Characterization of aberrant pathways activation and immune microenviroment of BK virus associated nephropathy.

Abstract

In the context of transplantation with the use of immunosuppressive drugs, BK virus infection has become the main cause of BK virus nephropathy(BKVN) in renal transplant recipients(KTRs). More importantly, BKVN may cause further allograft dysfunction and loss. However, the role of the immune microenvironment in the pathogenesis of BKVN remains unknown. Therefore, we collected microarray data of KTRs to elucidate the immune characteristics of BKVN. Via the CIBERSORT, we found that BKVN had relatively more activated memory CD4 T cells. Immunostaining showed that CD4+ and CD8+cells were significantly different between BKVN and stable allografts(STAs). In addition, the expression of immune-related genes(antigen presentation, cytotoxicity, and inflammation) was significantly higher in BKVN than in STAs. The results of gene set enrichment analysis(GSEA) and single-sample GSEA(ssGSEA) indicated that immune cell-,cytokine-,chemokine-, and inflammation-related pathways were significantly activated in BKVN, while metabolism- and renal development-related pathways were significantly downregulated in BKVN. In addition, the immune microenvironments of the peripheral blood in patients with BK viremia(BKV) or transplant kidney biopsy(TKB) with BKVN may be different. Overall, the immune microenvironment may play important roles in the occurrence and development of BKVN and provide a theoretical basis for preventing the occurrence of BKVN and finding novel treatments.