Background: Secukinumab is a fully human IgG1κ MoAb that selectively binds to IL-17A with high affinity, and it has been proven effective for the treatment of psoriasis. However, the immune response pathways and mechanisms during the treatment are still masked. Therefore, the current study was designed to investigate the potential immune response genes via bioinformatics approaches.
Methods: Gene expression data of severe plaque-type psoriasis was retrieved from the GEO database. Quantification of immune infiltration by ssGSEA and identification of differentially infiltrated immune cells were conducted to validate the treatment effect of secukinumab. After data processing, differentially expressed genes were identified between the treatment and untreated group. TC-seq was employed to analyze the trend of gene expression and clustering analysis. IL-17 therapeutic immune response genes were selected by taking the intersection of the genes inside the key cluster set and the MAD3-PSO geneset. Based on these therapeutic response genes, protein-protein interaction networks were built for key hub gene selection. These hub genes would work as potential immune response genes, and be validated via an external dataset.
Results: Enrichment scores calculated by ssGSEA illustrated that the immune infiltration level of T cells had a strong difference before and after medication, which validated the treatment effect of Secukinumab. 1525 genes that have significantly different expression patterns before and after treatment were extracted for further analysis, and the enrichment result shows that these genes have the function related to epidermal development, differentiation, and keratinocytes differentiation. After overlapping candidate genes with MAD3-PSO gene set, 695 genes were defined as anti-IL7A treatment immune response genes, which were mainly enriched in receptor signaling and IL-17 signaling pathways. Hub gene were pinpointed from the PPI network constructed by anti-IL7A treatment immune response genes, their expression pattern fits TC-seq gene expression pattern.
Conclusion: Our study revealed the potential anti-IL7A treatment immune response genes, and the central hub genes, which may act critical roles in Secukinumab, induced immune response. This would open up a novel and effective avenue for the treatment of psoriasis.
Keywords: Immune response; PPI; Secukinumab; Severe psoriasis.
© 2023. The Author(s).