Liu Siqi, Westra Johanna, Hu Shixian, Verschuuren Erik A M, van Kempen Léon C, van Baarle Debbie, Bos Nico A
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Front Transplant. 2024 Dec 18;3:1508419. doi: 10.3389/frtra.2024.1508419. eCollection 2024.
The acute rejection (AR) diagnosis depends on transbronchial biopsy, which is semi-invasive and not easily performed Our study used the Nanostring gene expression technology on PBMCs obtained from lung transplant recipients (LTRs) to search for biomarkers. We identified distinct differential gene profiles between patients with stable status (STA) and AR. Subsequently, we independently evaluated monocyte compositions in PBMCs using flow cytometry and assessed the levels of 7 chemokines in serum using Luminex. The 48 top differentially expressed genes (DEGs) were identified, utilizing a criterion of at least a 1.5-fold change between two groups, with a false discovery rate (FDR) -Adj < 0.05. Of these 48 genes, the top 10 genes with the highest fold changes and significant -values were selected for qPCR validation. CD68, ANXA1, ITGB, and IFI30 can be confirmed among the validated genes. A significantly lower percentage of CD14 + CD16- classical monocytes was observed in AR than in STA patients, which aligns with downregulated DEGs. Many of the DEGs were related to monocytes-macrophages and chemokines. Although these results still need to be confirmed in larger cohorts, they suggest that gene profiling of PBMC can help to identify markers related to AR in LTRs.
急性排斥反应（AR）的诊断依赖于经支气管活检，这种方法具有一定侵入性且操作不易。我们的研究利用纳米孔基因表达技术，对肺移植受者（LTRs）外周血单个核细胞（PBMCs）进行检测，以寻找生物标志物。我们确定了稳定状态（STA）患者和AR患者之间不同的差异基因谱。随后，我们使用流式细胞术独立评估PBMCs中的单核细胞组成，并使用Luminex技术检测血清中7种趋化因子的水平。利用两组之间至少1.5倍变化的标准，确定了48个差异表达最显著的基因（DEGs），错误发现率（FDR）-Adj < 0.05。在这48个基因中，选择了倍数变化最高且具有显著p值的前10个基因进行qPCR验证。在验证的基因中可以确认CD68、ANXA1、ITGB和IFI30。与STA患者相比，AR患者中CD14+CD16-经典单核细胞的比例显著降低，这与下调的DEGs一致。许多DEGs与单核细胞-巨噬细胞和趋化因子有关。虽然这些结果仍需在更大的队列中得到证实，但它们表明PBMC的基因谱分析有助于识别LTRs中与AR相关的标志物。
