Department of Nephrology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Front Immunol. 2022 Aug 26;13:978315. doi: 10.3389/fimmu.2022.978315. eCollection 2022.
Renin-angiotensin system inhibitors (RASi) are the first choice and basic therapy for the treatment of IgA nephropathy (IgAN) with proteinuria. However, approximately 40% of patients have no response to RASi treatment. The aim of this study was to screen potential biomarkers for predicting the treatment response of RASi in patients with IgAN.
We included IgAN patients who were treatment-naive. They received supportive treatment, including a maximum tolerant dose of RASi for 3 months. According to the degree of decrease in proteinuria after 3 months of follow-up, these patients were divided into a sensitive group and a resistant group. The plasma of the two groups of patients was collected, and the exosomes were extracted for high-throughput sequencing. The screening of hub genes was performed using a weighted gene co-expression network (WGCNA) and filtering differentially expressed genes (DEGs). We randomly selected 20 patients in the sensitive group and 20 patients in the resistant group for hub gene validation by real-time quantitative polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was used to evaluate hub genes that predicted the efficacy of the RASi response among the 40 validation patients.
After screening 370 IgAN patients according to the inclusion and exclusion criteria and the RASi treatment response evaluation, there were 38 patients in the sensitive group and 32 patients in the resistant group. IRAK1, ABCD1 and PLXNB3 were identified as hub genes by analyzing the high-throughput sequencing of the plasma exosomes of the two groups through WGCNA and DEGs screening. The sequencing data were consistent with the validation data showing that these three hub genes were upregulated in the resistant group compared with the sensitive group. The ROC curve indicated that IRAK1 was a good biomarker to predict the therapeutic response of RASi in patients with IgAN.
Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response of RASi in patients with IgAN.
肾素-血管紧张素系统抑制剂（RASi）是治疗伴有蛋白尿的 IgA 肾病（IgAN）的首选和基础治疗药物。然而，约有 40%的患者对 RASi 治疗无反应。本研究旨在筛选潜在的生物标志物，以预测 IgAN 患者 RASi 治疗的反应。
我们纳入了初治的 IgAN 患者。他们接受了支持性治疗，包括最大耐受剂量的 RASi 治疗 3 个月。根据 3 个月随访后蛋白尿下降程度，将这些患者分为敏感组和耐药组。收集两组患者的血浆，提取外泌体进行高通量测序。通过加权基因共表达网络分析（WGCNA）和筛选差异表达基因（DEGs）筛选出枢纽基因。我们随机选择 20 例敏感组患者和 20 例耐药组患者进行实时定量聚合酶链反应（qRT-PCR）验证枢纽基因。使用受试者工作特征（ROC）曲线评估 40 例验证患者中预测 RASi 反应疗效的枢纽基因。
根据纳入和排除标准以及 RASi 治疗反应评估，共筛选出 370 例 IgAN 患者，其中敏感组 38 例，耐药组 32 例。通过 WGCNA 和 DEGs 筛选分析两组血浆外泌体的高通量测序，鉴定出 IRAK1、ABCD1 和 PLXNB3 为枢纽基因。测序数据与验证数据一致，表明耐药组中这三个枢纽基因的表达水平高于敏感组。ROC 曲线表明 IRAK1 是预测 IgAN 患者 RASi 治疗反应的良好生物标志物。
血浆外泌体 IRAK1 可作为预测 IgAN 患者 RASi 治疗反应的潜在生物标志物。
