Garcia Jon Patrick T, Tayo Lemmuel L
School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, Manila 1002, Philippines.
School of Graduate Studies, Mapúa University, Manila 1002, Philippines.
Genes (Basel). 2024 Mar 22;15(4):393. doi: 10.3390/genes15040393.
Autoimmunity is defined as the inability to regulate immunological activities in the body, especially in response to external triggers, leading to the attack of the tissues and organs of the host. Outcomes include the onset of autoimmune diseases whose effects are primarily due to dysregulated immune responses. In past years, there have been cases that show an increased susceptibility to other autoimmune disorders in patients who are already experiencing the same type of disease. Research in this field has started analyzing the potential molecular and cellular causes of this interconnectedness, bearing in mind the possibility of advancing drugs and therapies for the treatment of autoimmunity. With that, this study aimed to determine the correlation of four autoimmune diseases, which are type 1 diabetes (T1D), psoriasis (PSR), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE), by identifying highly preserved co-expressed genes among datasets using WGCNA. Functional annotation was then employed to characterize these sets of genes based on their systemic relationship as a whole to elucidate the biological processes, cellular components, and molecular functions of the pathways they are involved in. Lastly, drug repurposing analysis was performed to screen candidate drugs for repositioning that could regulate the abnormal expression of genes among the diseases. A total of thirteen modules were obtained from the analysis, the majority of which were associated with transcriptional, post-transcriptional, and post-translational modification processes. Also, the evaluation based on KEGG suggested the possible role of T differentiation in the simultaneous onset of the four diseases. Furthermore, clomiphene was the top drug candidate for regulating overexpressed hub genes; meanwhile, prilocaine was the top drug for regulating under-expressed hub genes. This study was geared towards utilizing transcriptomics approaches for the assessment of microarray data, which is different from the use of traditional genomic analyses. Such a research design for investigating correlations among autoimmune diseases may be the first of its kind.
自身免疫被定义为机体无法调节免疫活动，尤其是对外部触发因素的反应，从而导致对宿主组织和器官的攻击。其结果包括自身免疫性疾病的发作，这些疾病的影响主要归因于免疫反应失调。在过去几年中，已经有案例表明，已经患有同类型疾病的患者对其他自身免疫性疾病的易感性增加。该领域的研究已经开始分析这种关联性的潜在分子和细胞原因，同时考虑推进治疗自身免疫性疾病的药物和疗法的可能性。据此，本研究旨在通过使用加权基因共表达网络分析（WGCNA）在数据集中识别高度保守的共表达基因，来确定四种自身免疫性疾病之间的相关性，这四种疾病分别是1型糖尿病（T1D）、银屑病（PSR）、系统性硬化症（SSc）和系统性红斑狼疮（SLE）。然后进行功能注释，根据这些基因集作为一个整体的系统关系来表征它们，以阐明它们所涉及的途径的生物学过程、细胞成分和分子功能。最后，进行药物重新利用分析，以筛选可重新定位的候选药物，这些药物可以调节疾病间基因的异常表达。分析共获得13个模块，其中大多数与转录、转录后和翻译后修饰过程相关。此外，基于京都基因与基因组百科全书（KEGG）的评估表明T细胞分化在这四种疾病同时发作中可能发挥的作用。此外，氯米芬是调节过表达中心基因的顶级候选药物；同时，丙胺卡因是调节低表达中心基因的顶级药物。本研究旨在利用转录组学方法评估微阵列数据，这与传统基因组分析的使用不同。这种研究自身免疫性疾病之间相关性的设计可能是首创的。
