Jiang Yanjie, Xie Yaxue, You Yingnan, Han Bo
Department of Pediatrics, Shandong Provincial Hospital, Shandong University Jinan, Shandong, China.
Department of Pediatrics, The Affiliated Taian City Central Hospital of Qingdao University Tai'an, Shandong, China.
Am J Transl Res. 2025 Mar 15;17(3):2339-2351. doi: 10.62347/CCVM6311. eCollection 2025.
While COVID-19 vaccination offers significant public health benefits, it also has potential risks, such as myocarditis. The mechanisms underlying myocarditis after COVID-19 vaccination remain poorly understood. The purpose of this study was to identify potential pathogenic genes and molecular pathways related with COVID-19 mRNA vaccine-associated myocarditis.
Differentially expressed genes (DEGs) were analyzed from a fulminant myocarditis (FM) cohort and a COVID-19 mRNA vaccination dataset. Shared DEGs were intersected, followed by functional enrichment, protein-protein interaction (PPI) network construction, and hub gene identification. Transcriptional and miRNA regulatory networks, as well as therapeutic drug predictions were also performed.
Eighty shared DEGs were identified by interacting DEGs from the FM cohort and the vaccination cohort, we identified. Functional enrichment analysis revealed that DEGs are significantly involved in immune cell-mediated responses, highlighting the critical role of immune dysregulation. PPI network analysis revealed three hub genes (CXCR3, NKG7, and GZMH), which may be involved in the pathogenesis of vaccine-associated myocarditis. Furthermore, transcriptional networks highlighted TBX21 and STAT4 as key regulators of all hub genes, while hsa-mir-146a-5p targeted CXCR3 and NKG7. PhIP, a compound targeting CXCR3 and NKG7, emerged as a potential therapeutic candidate.
This study implicates immune dysregulation driven by CXCR3, NKG7, and GZMH in post-vaccination myocarditis, supported by regulatory networks and therapeutic insights using a bioinformatics analysis. These findings advance mechanistic understanding of this rare adverse event and propose potential treatment strategy for further investigation.
虽然新冠病毒疫苗接种对公众健康有显著益处，但也存在潜在风险，如心肌炎。新冠病毒疫苗接种后心肌炎的潜在机制仍知之甚少。本研究的目的是确定与新冠病毒信使核糖核酸（mRNA）疫苗相关心肌炎相关的潜在致病基因和分子途径。
从暴发性心肌炎（FM）队列和新冠病毒mRNA疫苗接种数据集分析差异表达基因（DEG）。对共享的DEG进行交集分析，随后进行功能富集、蛋白质-蛋白质相互作用（PPI）网络构建和枢纽基因鉴定。还进行了转录和微小RNA（miRNA）调控网络以及治疗药物预测。
通过对FM队列和我们确定的疫苗接种队列中的DEG进行相互作用，确定了80个共享的DEG。功能富集分析表明，DEG显著参与免疫细胞介导的反应，突出了免疫失调的关键作用。PPI网络分析揭示了三个枢纽基因（CXCR3、NKG7和GZMH），它们可能参与疫苗相关心肌炎的发病机制。此外，转录网络突出显示TBX21和STAT4是所有枢纽基因的关键调节因子，而hsa-mir-146a-5p靶向CXCR3和NKG7。一种靶向CXCR3和NKG7的化合物PhIP成为潜在的治疗候选物。
本研究表明，通过生物信息学分析的调控网络和治疗见解支持，CXCR3、NKG7和GZMH驱动的免疫失调与疫苗接种后心肌炎有关。这些发现推进了对这种罕见不良事件机制的理解，并提出了潜在的治疗策略以供进一步研究。
