Department of Rheumatology and Immunology, Affiliated Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China.
Department of Hepatobiliary and Pancreatic Surgery, Conversion Therapy Center for Hepatobiliary and Pancreatic Tumors, First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, China.
Int J Rheum Dis. 2023 May;26(5):895-906. doi: 10.1111/1756-185X.14668. Epub 2023 Mar 27.
To investigate the novel key genes and biological processes that may lead to primary Sjögren' s syndrome (pSS).
We downloaded datasets about peripheral blood samples of pSS patients and healthy controls (GSE51092, GSE84844, and GSE66795) from Gene Expression Omnibus database. The weighted co-expression network analysis and differential expression analysis first were implemented. After that, protein-protein network interaction and Support Vector Machines were applied in the meantime to take intersection for key genes. Moreover, we conducted immune cell infiltration analysis to explore the relationship between the gene expression and concentration of immune cells in peripheral blood. Lastly, the expression of key genes was verified in pSS patients and murine models by reverse-transcription polymerase chain reaction. Meanwhile, correlation analysis of gene expression and disease activity was also performed.
Only 1 key gene, interferon induced with helicase c domain 1 (IFIH1), was identified to be both significantly up-regulated and important for the diagnosis of pSS. The increased expression of IFIH1 in peripheral blood was confirmed in data sets, patients and non-obese diabetic (NOD) mice. Its expression was correlated with disease activity in patients as well. In addition, the IFIH1 expression was also increased in spleen and salivary glands infiltrated with lymphocytes in NOD mice. Furthermore, immune cell infiltration analysis showed that the expression of IFIH1 was positively correlated with the proportion of memory B cells and activated dendritic cells, and negatively correlated with the proportion of macrophage M0.
Here, bioinformatics analyses and experimental assays were performed to provide a new insight for understanding of pSS. IFIH1 may be a new diagnostic marker or therapeutic target for pSS.
探索可能导致原发性干燥综合征（pSS）的新的关键基因和生物学过程。
我们从基因表达综合数据库中下载了 pSS 患者和健康对照者外周血样本的数据集（GSE51092、GSE84844 和 GSE66795）。首先进行加权共表达网络分析和差异表达分析。然后，同时应用蛋白质-蛋白质网络互作和支持向量机对关键基因进行交集处理。此外，我们还进行了免疫细胞浸润分析，以探讨基因表达与外周血免疫细胞浓度之间的关系。最后，通过逆转录聚合酶链反应在 pSS 患者和鼠模型中验证了关键基因的表达，并进行了基因表达与疾病活动相关性的分析。
仅鉴定出 1 个关键基因，即干扰素诱导的含有螺旋酶 C 结构域 1（IFIH1），该基因在 pSS 患者中显著上调，且对 pSS 的诊断具有重要意义。IFIH1 在患者和非肥胖型糖尿病（NOD）小鼠外周血中的表达增加在多个数据集、患者和 NOD 小鼠中得到了验证。其表达与患者的疾病活动度也相关。此外，在 NOD 小鼠的脾脏和唾液腺浸润淋巴细胞中，IFIH1 的表达也增加了。此外，免疫细胞浸润分析表明，IFIH1 的表达与记忆 B 细胞和活化树突状细胞的比例呈正相关，与 M0 型巨噬细胞的比例呈负相关。
本研究通过生物信息学分析和实验验证，为理解 pSS 提供了新的视角。IFIH1 可能是 pSS 的一个新的诊断标志物或治疗靶点。
