Aberrant formation of the neutrophil extracellular trap and the expression of the PLEKHA1 in systemic lupus erythematosus and ulcerative colitis

Abstract

Systemic lupus erythematosus (SLE) and ulcerative colitis (UC) are both chronic autoimmune diseases with unclear shared mechanisms, largely due to limited mechanistic studies and clinical research cohorts. Transcriptome datasets from the Gene Expression Omnibus (GEO) database were analyzed for SLE and UC, identifying differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) identified significant module genes, including PLEKHA1. The diagnostic potential of PLEKHA1 was confirmed using machine-learning algorithms and real-time fluorescence quantitative PCR (RT-PCR) in clinical samples. Additionally, the study explored the link between PLEKHA1 and neutrophil extracellular trap (NET) formation. Our analyses identified transcriptional signatures associated with neutrophil degranulation and NET formation pathways in the peripheral blood of both SLE and UC, a perspective not previously explored. PLEKHA1 was identified as a promising biomarker that may impact NET formation. Pathway enrichment analyses indicated that PLEKHA1 plays a regulatory role in NET formation in both diseases. This study provides novel transcriptional evidence by proposing neutrophil degranulation and NET formation as common pathways in SLE and UC, with PLEKHA1 acting as a shared diagnostic gene. PLEKHA1 may regulate neutrophil activation and immune response, influencing NET formation and neutrophil degranulation in SLE patients' peripheral blood.

Keywords: Biomarker; Lasso regression; Machine learning; Neutrophil extracellular trap; Systemic lupus erythematosus; Ulcerative colitis.