Integrated Analysis of Intersecting Neutrophil Signatures in Behçet's Disease and Inflammatory Bowel Disease

ABSTRACT Introduction Behçet's disease (BD) and inflammatory bowel disease (IBD) are chronic inflammatory diseases characterized by immune system dysregulation. The critical role of neutrophils in these conditions is increasingly recognized. This study aimed to identify a shared set of neutrophils differentially expressed genes (NDEGs) to aid in the differential diagnosis of the two diseases. Methods Bioinformatics analysis of GEO data combined with WGCNA identified 65 key NDEGs. Functional enrichment and immune infiltration analyses were conducted. RT‐qPCR validated six hub NDEGs in neutrophils from IBD and BD patients. Serum CD226 levels were measured by ELISA, and a ROC curve assessed its diagnostic value. Additionally, neutrophils were stimulated with patient serum, followed by Western blot analysis. Results Immune infiltration analysis showed higher blood neutrophil levels in BD than in IBD. Neutrophil sequencing identified NDEGs upregulated in BD but downregulated in IBD, linked to T‐cell receptor pathways. RT‐PCR confirmed elevated FYN, CD99, SKAP1, and CD226 in BD neutrophils, while KLRG1 and MATK were higher in IBD. ELISA showed increased serum CD226 in BD. Western blot revealed higher Elastase and PAD4 in BD‐stimulated neutrophils, while CXCL11 was elevated in IBD‐stimulated neutrophils. Conclusions Our findings suggest that BD and IBD neutrophils may have distinct functional states, potentially linked to differential T‐cell interactions. These insights highlight neutrophils' diverse roles in immune dysregulation and their potential as diagnostic markers and therapeutic targets.