Liu Changjian, Ge Yongpeng
Department of Rheumatology, the Key Laboratory of Myositis, China-Japan Friendship Hospital, Beijing, People's Republic of China.
Int J Gen Med. 2024 Nov 14;17:5261-5271. doi: 10.2147/IJGM.S490294. eCollection 2024.
Interstitial lung disease (ILD) is one of the significant complications of dermatomyositis (DM), but the mechanisms by which it occurs remain incompletely elucidated. This study aimed to explore further the possible genetic mechanisms by which this complication occurs.
Gene expression profiles for DM (GSE39454, GSE46239, GSE143323) and ILD (GSE32537, GSE110147, GSE150910) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying common differentially expressed genes (DEGs) to DM and ILD using the "limma" R package and the "VennDiagram" R package, functional annotation, relationship to immune cell infiltration, identification of transcription factors (TFs), we also collected clinical cases of DM-associated ILD (DM-ILD), including 3 cases of rapidly progressive ILD (RP-ILD) and 3 cases of none-RP-ILD, and explored whether there were differences in serum lymphocyte subpopulations.
A total of 4 common DEGs (SLAMF7, SPP1, TDO2, and VCAM1) were screened and Gene Ontology (GO) enrichment analysis showed that these genes were mainly enriched in T cell activation, regulation of lymphocyte activation, lymphocyte differentiation, leukocyte proliferation and regulation of T cell activation. In terms of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the three significantly enriched pathways were the PI3K-Akt signaling pathway, MAPK signaling pathway, and Cytokine-cytokine receptor interaction. In lung and muscle tissues, 21 and 3 TFs may regulate the expression of these genes, respectively. Finally, by analysing the serum lymphocyte subpopulations, we also found a decrease in the absolute number of CD8+ T cells and an increase in the CD4+ /CD8+ T cell ratio in DM combined with RP-ILD.
These common pathways and key genes may provide new ideas for further research into DM-ILD.
间质性肺病（ILD）是皮肌炎（DM）的重要并发症之一，但其发病机制仍未完全阐明。本研究旨在进一步探索该并发症发生的可能遗传机制。
从基因表达综合数据库（GEO）下载DM（GSE39454、GSE46239、GSE143323）和ILD（GSE32537、GSE110147、GSE150910）的基因表达谱。使用“limma”R包和“VennDiagram”R包鉴定DM和ILD的共同差异表达基因（DEG）后，进行功能注释、与免疫细胞浸润的关系分析、转录因子（TF）鉴定，我们还收集了DM相关ILD（DM-ILD）的临床病例，包括3例快速进展性ILD（RP-ILD）和3例非RP-ILD，并探讨血清淋巴细胞亚群是否存在差异。
共筛选出4个共同DEG（信号淋巴细胞激活分子家族7、分泌型磷蛋白1、犬尿氨酸2,3-双加氧酶和血管细胞黏附分子1），基因本体（GO）富集分析表明这些基因主要富集于T细胞活化、淋巴细胞活化调节、淋巴细胞分化、白细胞增殖和T细胞活化调节。在京都基因与基因组百科全书（KEGG）通路方面，三个显著富集的通路是磷脂酰肌醇3-激酶-蛋白激酶B信号通路、丝裂原活化蛋白激酶信号通路和细胞因子-细胞因子受体相互作用。在肺和肌肉组织中，分别有21个和3个TF可能调节这些基因的表达。最后，通过分析血清淋巴细胞亚群，我们还发现DM合并RP-ILD时CD8 + T细胞绝对数减少，CD4 + /CD8 + T细胞比值增加。
这些共同通路和关键基因可能为进一步研究DM-ILD提供新思路。
