Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Institute of Urology, Capital Medical University, Beijing 100020, China.
J Immunol Res. 2022 Jul 31;2022:6934744. doi: 10.1155/2022/6934744. eCollection 2022.
BK virus-associated nephropathy (BKVN) remains a major infectious complication due to powerful immunosuppression in kidney transplant recipients, and its histologic appearance can mimic rejection, leading to diagnostic and treatment dilemmas thus molecular diagnostic methods would be beneficial. We collected gene expression profiles of 169 kidney biopsies taken from BKVN, rejection, and stable functioning allografts, based on single sample gene set enrichment analysis and random forest algorithm, and three hallmark activities associated with DNA damage and proliferation were found to be relatively specific in BKVN. Subsequently, weighted gene co-expression network analysis and support vector machines (SVM) algorithm identified as a robust and promising biomarker with high accuracy in both training and validation cohorts (AUC =0.938, 0.977, respectively). Besides, potential drugs for BKVN treatment such as mepacrine were discovered, which may contribute to targeted antiviral therapy and effective patient management rather than simply reducing the doses of immunosuppressive agents in clinical practice. (retinoblastoma binding protein 7) serves as component of serval complexes that regulate chromatin metabolism and functions in affecting DNA replication and controlling cell proliferation. In this research, upregulation of was found to be associated with the higher infiltration of CD8 naïve T, iTreg, and neutrophil cells and the lower amounts of Th1, central memory T, NKT, CD8 T, and dendritic cells. Moreover, the infiltration of Th1, Th17, and NKT cells was steadily different between BKVN and rejection allografts through immune cell assessment. In conclusion, we identified and verified as a molecular biomarker for BKVN diagnosis, which demonstrated great distinguishing ability with allograft rejection and would support clinical decision-making.
BK 病毒相关性肾病 (BKVN) 仍然是肾移植受者因强力免疫抑制而导致的主要感染性并发症，其组织学表现可模仿排斥反应，导致诊断和治疗困境，因此分子诊断方法将是有益的。我们收集了来自 BKVN、排斥和稳定功能同种异体移植物的 169 个肾活检的基因表达谱，基于单样本基因集富集分析和随机森林算法，发现与 DNA 损伤和增殖相关的三个标志性活动在 BKVN 中相对特异。随后，加权基因共表达网络分析和支持向量机 (SVM) 算法确定 为一种稳健且有前途的生物标志物，在训练和验证队列中均具有高准确性 (AUC=0.938，0.977)。此外，还发现了治疗 BKVN 的潜在药物，如米帕林，这可能有助于靶向抗病毒治疗和有效患者管理，而不是简单地减少免疫抑制剂在临床实践中的剂量。 (视网膜母细胞瘤结合蛋白 7) 作为调节染色质代谢的几个复合物的组成部分，在影响 DNA 复制和控制细胞增殖方面发挥作用。在这项研究中，上调 与 CD8 幼稚 T、iTreg 和中性粒细胞的更高浸润以及 Th1、中央记忆 T、NKT、CD8 T 和树突状细胞的更低数量有关。此外，通过免疫细胞评估，BKVN 和排斥同种异体移植物之间 Th1、Th17 和 NKT 细胞的浸润也存在稳定差异。总之，我们确定并验证 作为 BKVN 诊断的分子生物标志物，其对同种异体移植排斥具有很强的鉴别能力，并将支持临床决策。
