Shared and different immune molecular signatures of lung transcriptome between connective tissue disease associated and idiopathic pulmonary arterial hypertension

Background Pulmonary arterial hypertension (PAH) is one of severe pulmonary circulatory complications and could be idiopathic or associated with connective tissue diseases (CTD). Immune mechanism has been discovered as an important mechanism in both idiopathic PAH (IPAH) and CTD-associated PAH (CTD-PAH). However, differences in immune response between IPAH and CTD-PAH need further exploration. This study compared the immune features of IPAH and CTD-PAH with integrated transcriptomics data from lung tissue. Methods Microarray data (GSE48149, GSE113439, and GSE117261) were downloaded from NCBI GEO. Differentially expressed genes (DEGs) were screened by limma package. Functional enrichment analysis and Gene set enrichment analysis (GSEA) were performed. Weighted gene co-expression network analysis (WGCNA) was conducted to screen immune-related module correlated with the two diseases. A specific Protein-Protein Interaction (PPI) network based on screened modules and the most representative pathway with the disease were visualized using Pathview. Potential targeted drug were selected based on selected DEGs and Drugbank database. Results Transcriptome data from 19 CTD-PAH patients, 46 IPAH patients and 45 healthy controls (HCs) were collected and integrated. 394 and 207 DEGs were identified in CTD-PAH and IPAH respectively and 111 shared DEGs were found. Inflammatory response were found enriched in shared DEGs, while CTD-PAH-specific pathways were more relevant to innate immune response. WGCNA analysis and following enrichment identified TNF signaling pathway correlated with CTD-PAH and Th1/Th2 differentiation pathway correlated with IPAH. Hub genes found in CTD-PAH included IL6 and CCL2 , and in IPAH, CCL5 and IFNG were found to potentially play important roles. Possible drugs targeting discovered genes included adalimumab in CTD-PAH and emapalumab in IPAH. Conclusions This study revealed the shared and different characteristics of transcriptome between CTD-PAH and IPAH, particularly in immune response. Our results provide more basis for further research design in the pathophysiologic processes in lung and potential drug discovery.