Xu Li, Wu Tao, Zhang Wu, Xiao Songlin
Department of Cardiovascular Medicine, People's Hospital of Anyue County Ziyang 642350, Sichuan, PR China.
Am J Clin Exp Immunol. 2025 Apr 25;14(2):68-85. doi: 10.62347/KGZR5419. eCollection 2025.
Systemic lupus erythematosus (SLE) and dilated cardiomyopathy (DCM) are closely linked biologically, especially regarding immune responses. However, key biomarkers mediating the onset and development of both diseases are still lacking. This study uses bioinformatic methods to analyse the immune microenvironment of the ventricles of DCM patients and to search for biomarkers related to DCM and SLE.
Single-cell and bulk transcriptomic data for DCM were obtained from the GEO database, while GWAS data for SLE were obtained from the FinnGen database. The SMR method was used to identify genetic variants in the ventricles associated with SLE. Differential analysis was used to detect genes specific to monocyte-macrophages. Subsequently, a combination of machine learning algorithms was employed to select hub genes. Finally, small molecule drugs targeting the hub genes were retrieved from the DGIdb database.
Mononuclear macrophages were found to be significantly infiltrated in dilated cardiomyopathy (DCM) samples. Seven key genes (HLA-DQB1, CD52, FCER1A, etc.) were identified by cross-tabulation analysis, of which FCER1A was the best-performing (AUC 0.8-0.9) among ten machine learning models. Validation of multiple datasets showed that FCER1A was highly expressed in the DCM group, was mainly involved in the immune cell activation pathway, and strongly interacted with other cells in the myocardial microenvironment through the MK/PROS pathway. The gene was highly expressed in the middle and late stages of monocyte-macrophage differentiation and was associated with drugs such as benzathine penicillin polylysine and omalizumab.
FCER1A was found to be a key differentially expressed gene in mononuclear macrophages in DCM myocardial tissue, and its significantly high expression was closely associated with immune cell activation in the myocardial microenvironment, which lays a theoretical foundation for immunotherapy of DCM and requires further clinical validation.
系统性红斑狼疮（SLE）与扩张型心肌病（DCM）在生物学上密切相关，尤其是在免疫反应方面。然而，介导这两种疾病发生和发展的关键生物标志物仍然缺乏。本研究采用生物信息学方法分析DCM患者心室的免疫微环境，并寻找与DCM和SLE相关的生物标志物。
从GEO数据库获得DCM的单细胞和批量转录组数据，而从FinnGen数据库获得SLE的全基因组关联研究（GWAS）数据。使用SMR方法鉴定与SLE相关的心室遗传变异。差异分析用于检测单核细胞-巨噬细胞特异性基因。随后，采用机器学习算法组合来选择枢纽基因。最后，从DGIdb数据库中检索靶向枢纽基因的小分子药物。
发现单核巨噬细胞在扩张型心肌病（DCM）样本中显著浸润。通过交叉分析确定了七个关键基因（HLA-DQB1、CD52、FCER1A等），其中FCER1A在十个机器学习模型中表现最佳（AUC为0.8 - 0.9）。多个数据集的验证表明，FCER1A在DCM组中高表达，主要参与免疫细胞激活途径，并通过MK/PROS途径与心肌微环境中的其他细胞强烈相互作用。该基因在单核细胞-巨噬细胞分化的中晚期高表达，并与苄星青霉素聚赖氨酸和奥马珠单抗等药物相关。
发现FCER1A是DCM心肌组织中单核巨噬细胞的关键差异表达基因，其显著高表达与心肌微环境中的免疫细胞激活密切相关，为DCM的免疫治疗奠定了理论基础，需要进一步的临床验证。
