Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Department of Virology, School of Public Health, Tehran University of Medical Sciences, 14155-6446, Tehran, Iran.
Immunol Res. 2021 Apr;69(2):196-204. doi: 10.1007/s12026-021-09186-4. Epub 2021 Mar 30.
Systemic lupus erythematosus (SLE) is an autoimmune disease that involves several organ systems. Although B cells play a key role in SLE pathogenesis, the mechanisms behind B cell dysregulation in SLE development remained controversial. Finding the modules containing highly co-expressed genes in B cells could explain biological pathways involved in the pathogenesis of SLE, which may further support the reasons for the altered function of B cells in SLE disease. A total of three microarray gene expression datasets were downloaded from Gene Expression Omnibus. SLE samples were prepared from the purified B lymphocyte cells of the patients who have not received immunosuppressive drugs as well as high dose immunocytotoxic therapies or steroids. A weighted gene co-expression network was then constructed to find the relevant modules implicated in the SLE progression. Among 17 identified modules, 3 modules were selected through mapping to STRING and finding the ones that had highly connection at the protein level. These modules clearly indicate the involvement of several pathways in the pathogenesis of SLE including viral infection, adaptive immune response, and innate immune response in B lymphocytes. The WGCN analysis further revealed the co-expressed genes involved in both innate and adaptive immune systems. Mix infections and primary immunodeficiency might also dysregulate B lymphocytes, which may facilitate SLE development. As such, identifying novel biomarkers and pathways in lupus would be of importance.
系统性红斑狼疮（SLE）是一种涉及多个器官系统的自身免疫性疾病。虽然 B 细胞在 SLE 发病机制中起关键作用，但 SLE 发展中 B 细胞失调的机制仍存在争议。发现 B 细胞中高度共表达基因的模块可以解释 SLE 发病机制中涉及的生物学途径，这可能进一步支持 B 细胞在 SLE 疾病中改变功能的原因。总共从基因表达综合数据库下载了三个微阵列基因表达数据集。SLE 样本是从未接受免疫抑制药物、大剂量免疫细胞毒性治疗或类固醇治疗的患者的纯化 B 淋巴细胞中制备的。然后构建加权基因共表达网络以寻找与 SLE 进展相关的相关模块。在鉴定出的 17 个模块中，通过映射到 STRING 并找到在蛋白质水平上具有高度连接的模块，选择了 3 个模块。这些模块清楚地表明，包括病毒感染、适应性免疫反应和 B 淋巴细胞中的固有免疫反应在内的几种途径参与了 SLE 的发病机制。WGCN 分析还揭示了参与固有和适应性免疫系统的共表达基因。混合感染和原发性免疫缺陷也可能使 B 细胞失调，这可能促进 SLE 的发展。因此，鉴定狼疮中的新型生物标志物和途径非常重要。
