Zhang Haidong, Li Sicong, Deng Zhenling, Wang Yue
Department of Nephrology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
J Inflamm Res. 2024 Dec 21;17:11357-11373. doi: 10.2147/JIR.S496138. eCollection 2024.
Immunoglobulin A nephropathy (IgAN) and lupus nephritis (LN) are the most prevalent primary and secondary glomerular diseases, respectively, with several similarities in clinical presentations. Common pathogenic mechanisms in IgAN and LN have been well investigated by previous studies. However, the manifestation mechanism of these two independent diseases carrying distinct immunofluorescent pathological features is still unknown considering the similarities between them. Therefore, differences in pathogenic mechanisms between IgAN and LN were compared in this study.
R packages were used for processing the glomerular gene expression datasets acquired from the Gene Expression Omnibus (GEO) database. Least Absolute Selection and Shrinkage Operator (LASSO) and multivariate logistic regression analysis were used to construct models predicting IgAN and LN. Cibersort was used to process the immune cell infiltration analysis. Immunochemistry was used to validate the findings by bioinformatics analysis.
In the predicting models based on differentially expressed genes (DEG) and weighted correlation network analysis (WGCNA), retinoic acid receptor γ (RARG) and prolactin releasing hormone (PRLH) were independent risk factors for IgAN, and HECT domain and RCC1-like domain-containing protein 5 (HERC5) and interferon stimulated exonuclease gene 20 (ISG20) were independent risk factors for LN. Gene Ontology (GO) analysis revealed that DEGs mostly correlated to IgAN were enriched in ligand-receptor activity-induced cellular growth and development, while DEGs mostly correlated to LN were enriched in nucleic acid/nucleotide binding-induced type I interferon-related activity and response to virus infection. Immune infiltration analysis showed CD4+ T-cells and M2 macrophage abundance in the glomerular compartment in IgAN and LN, respectively. Immunochemistry validated the predicting models for IgAN and LN and revealed different expression patterns of RARG, PRLH, HERC5, and ISG20.
We investigated key differences in the pathogenesis between IgAN and LN and provided validated predicting models to distinguish IgAN and LN. RARG and PRLH, HERC5 and ISG20 might play an essential role in the formation of IgAN and LN, respectively.
免疫球蛋白A肾病（IgAN）和狼疮性肾炎（LN）分别是最常见的原发性和继发性肾小球疾病，临床表现有若干相似之处。既往研究已对IgAN和LN的常见致病机制进行了充分研究。然而，鉴于这两种独立疾病之间的相似性，其具有不同免疫荧光病理特征的表现机制仍不清楚。因此，本研究比较了IgAN和LN致病机制的差异。
使用R软件包处理从基因表达综合数据库（GEO）获取的肾小球基因表达数据集。采用最小绝对收缩和选择算子（LASSO）及多变量逻辑回归分析构建预测IgAN和LN的模型。使用Cibersort进行免疫细胞浸润分析。采用免疫化学方法通过生物信息学分析验证研究结果。
在基于差异表达基因（DEG）和加权基因共表达网络分析（WGCNA）的预测模型中，视黄酸受体γ（RARG）和催乳素释放激素（PRLH）是IgAN的独立危险因素，含HECT结构域和RCC1样结构域蛋白5（HERC5）及干扰素刺激核酸外切酶基因20（ISG20）是LN的独立危险因素。基因本体（GO）分析显示，与IgAN大多相关的DEG在配体-受体活性诱导的细胞生长和发育中富集，而与LN大多相关的DEG在核酸/核苷酸结合诱导的I型干扰素相关活性和对病毒感染的反应中富集。免疫浸润分析显示，IgAN和LN的肾小球中分别有CD4+T细胞和M2巨噬细胞富集。免疫化学验证了IgAN和LN的预测模型，并揭示了RARG、PRLH、HERC5和ISG20的不同表达模式。
我们研究了IgAN和LN发病机制的关键差异，并提供了经过验证的预测模型以区分IgAN和LN。RARG和PRLH、HERC5和ISG20可能分别在IgAN和LN的形成中起重要作用。
