Diagnostic Biomarkers and Immune Infiltration in Patients With T Cell-Mediated Rejection After Kidney Transplantation

被引:10
作者
Zhou, Hai [1 ]
Lu, Hongcheng [2 ]
Sun, Li [2 ]
Wang, Zijie [2 ]
Zheng, Ming [2 ]
Hang, Zhou [1 ]
Zhang, Dongliang [1 ]
Tan, Ruoyun [2 ]
Gu, Min [1 ]
机构
[1] Nanjing Med Univ, Dept Urol, Affiliated Hosp 2, Nanjing, Peoples R China
[2] Nanjing Med Univ, Dept Urol, Affiliated Hosp 1, Nanjing, Peoples R China
基金
中国国家自然科学基金;
关键词
kidney transplantation; T cell-mediated rejection; diagnostic biomarkers; immune infiltration; bioinformatic analysis; ACTIVATION; EXPRESSION; SURVIVAL; BIOPSIES; DISEASES; SUBSETS; PROFILE; MEMORY;
D O I
10.3389/fimmu.2021.774321
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T cell-mediated rejection (TCMR) is an important rejection type in kidney transplantation, characterized by T cells and macrophages infiltration. The application of bioinformatic analysis in genomic research has been widely used. In the present study, Microarray data was analyzed to identify the potential diagnostic markers of TCMR in kidney transplantation. Cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT) was performed to determine the distribution of immune cell infiltration in the pathology. Totally 129 upregulated differently expressed genes (DEGs) and 378 downregulated DEGs were identified. The GO and KEGG results demonstrated that DEGs were mainly associated with pathways and diseases involved in immune response. The intersection of the two algorithms (PPI network and LASSO) contains three overlapping genes (CXCR6, CXCL13 and FCGR1A). After verification in GSE69677, only CXCR6 and CXCL13 were selected. Immune cells Infiltration analysis demonstrated that CXCR6 and CXCL13 were positively correlated with gamma delta T cells (p < 0.001), CD4(+) memory activated T cells (p < 0.001), CD8(+) T cells (p < 0.001) and M1 macrophages (p = 0.006), and negatively correlated with M2 macrophages (p < 0.001) and regulatory T cells (p < 0.001). Immunohistochemical staining and image analysis confirmed the overexpression of CXCR6 and CXCL13 in human allograft TCMR samples. CXCR6 and CXCL13 could be diagnostic biomarkers of TCMR and potential targets for immunotherapy in patients with TCMR.
引用
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页数:11
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