Research Paper Volume 12, Issue 14 pp 14434—14451

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

Yongguang Liu1, *, , Song Zhou1, *, , Jianmin Hu1, , Wentao Xu1, , Ding Liu1, , Jun Liao1, , Guorong Liao1, , Zefeng Guo1, , Yuzhu Li1, , Siqiang Yang1, , Shichao Li1, , Hua Chen1, , Ying Guo1, , Ming Li1, , Lipei Fan1, , Liuyang Li1, , Anqi Lin1, , Ming Zhao1, ,

  • 1 Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
* Equal contribution

Received: March 3, 2020       Accepted: May 27, 2020       Published: July 13, 2020      

https://doi.org/10.18632/aging.103486
How to Cite

Copyright © 2020 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Abbreviations

BKVN: BK virus nephropathy; KTRs: renal transplant recipients; STAs: stable allografts; GSEA: gene set enrichment analysis; ssGSEA: single-sample gene set enrichment analysis; BKV: BK viremia; TKB: transplant kidney biopsy; NKs: NK cells; PTX3: pentraxin 3; IL: interleukin; CD: Cluster of Differentiation; TNF: tumor necrosis factor; PFP: perforin; GEO: Gene Expression Omnibus; PB: peripheral blood; CYT: cytotoxicity; APP: antigen processing and presentation; MSigDB: The Molecular Signatures Database; GO: gene ontology; BP: biological process; MF: molecular function; CC: cellular component; KEGG: Kyoto Encyclopedia of Genes and Genomes.