Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2020 Aug 20;11:1795. doi: 10.3389/fimmu.2020.01795. eCollection 2020.
Immunoglobulin G4-related disease (IgG4-RD) is a newly defined disease entity, while the exact pathogenesis is still not clear. Identifying the characters of IgG4-RD in proteomic and transcriptomic aspects will be critical to investigate the potential pathogenic mechanisms of IgG4-RD. We performed proteomic analysis realized with iTRAQ technique for serum samples from eight treatment-naive IgG4-RD patients and eight healthy volunteers, and tissue samples from two IgG4-RD patients and two non-IgG4-RD patients. Transcriptomic data (GSE40568 and GSE66465) was obtained from the GEO Dataset for validation. The weighted correlation network analysis (WGCNA) was applied to detect the gene modules correlated with IgG4-RD. KEGG pathway analysis was used to investigate pathways enriched in IgG4-RD samples. As a result, a total of 980 differentially expressed proteins (DEPs) in tissue and 94 DEPs in serum were identified between IgG4-RD and control groups. Three hundred fifty-four and two hundred forty-seven genes that most correlated with IgG4-RD were detected by WGCNA analysis in tissue and PBMC, respectively. We also found that DEPs in IgG4-RD samples were enriched in several immune-related activities including bacterial/viral infections and platelet activation as well as some immune related signaling pathways. In conclusion, we identified multiple processes/factors and several signaling pathways that may involve in the IgG4-RD pathogenesis, and found out some potential therapeutic targets for IgG4-RD.
免疫球蛋白 G4 相关疾病（IgG4-RD）是一种新定义的疾病实体，而确切的发病机制仍不清楚。在蛋白质组学和转录组学方面识别 IgG4-RD 的特征对于研究 IgG4-RD 的潜在发病机制至关重要。我们使用 iTRAQ 技术对 8 名未经治疗的 IgG4-RD 患者和 8 名健康志愿者的血清样本以及 2 名 IgG4-RD 患者和 2 名非 IgG4-RD 患者的组织样本进行了蛋白质组分析。为了验证，从 GEO 数据集获得了转录组数据（GSE40568 和 GSE66465）。应用加权相关网络分析（WGCNA）检测与 IgG4-RD 相关的基因模块。KEGG 途径分析用于研究 IgG4-RD 样本中富集的途径。结果，在组织和血清中分别鉴定出 IgG4-RD 与对照组之间的 980 个差异表达蛋白（DEPs）和 94 个 DEPs。通过 WGCNA 分析在组织和 PBMC 中分别检测到与 IgG4-RD 最相关的 354 个和 247 个基因。我们还发现，IgG4-RD 样本中的 DEPs 富集于几种免疫相关活性，包括细菌/病毒感染和血小板激活以及一些免疫相关信号通路。总之，我们鉴定了多个可能参与 IgG4-RD 发病机制的过程/因子和几个信号通路，并发现了一些 IgG4-RD 的潜在治疗靶点。
