Distinct transcriptional profile of blood mononuclear cells in Behçet’s disease: insights into the central role of neutrophil chemotaxis

Abstract

Objectives Both innate and adaptive immune responses are reportedly increased in Behcet’s disease (BD), a chronic-relapsing systemic vasculitis lying at the intersection between autoinflammation and autoimmunity. To further study pathophysiologic molecular mechanisms operating in BD we searched for transcriptome-wide changes in blood mononuclear cells from these patients. Methods We performed 3’ mRNA next generation sequencing-based genome-wide transcriptional profiling followed by analysis of differential expression signatures, KEGG pathways, GO biological processes and transcription factor signatures. Results Differential expression analysis clustered the transcriptomes of 13 patients and one healthy subject apart from those of 10 healthy age/gender-matched controls and one patient. Among the total of 17,591 expressed protein coding genes, 209 and 31 genes were significantly up- and down-regulated, respectively, in BD versus controls by at least 2-fold. The most up-regulated genes comprised an abundance of CC- and CXC-chemokines. Remarkably, the 5 out of top 10 up-regulated biological processes involved leukocyte recruitment to peripheral tissues, especially for neutrophils. Moreover, NF-kB, TNF and IL-1 signaling pathways were prominently enhanced in BD, while transcription factor activity analysis suggested that the NF-kB p65/RELA subunit action underlies the observed differences in the BD transcriptome. Conclusion This RNA-sequencing analysis in PBMCs derived from patients with BD does not support a major pathogenetic role of adaptive immunity-driven mechanisms, but clearly points to the action of aberrant innate immune responses with a central role of up-regulated neutrophil chemotaxis.

The transcriptional profiling identifies hub genes in immune subsets of patients with Behçet's syndrome

“…This study analysed immune subsets of BS patients of mRNA microarray Transcriptional profiling hub genes in BS / J. Zou neutrophils and M1 macrophages are the features of BS (26,27). Consistent with our findings, a recent mRNA sequencing study identified that most DEGs comprised an abundance of CC-and CXCchemokines in leucocyte recruitment to peripheral tissues, especially neutrophils (28). Similarly, a previous microarray study in whole blood cells showed a strong enrichment of genes involved in inflammation, IL-and TLR-signalling, with high levels of chemokines (e.g., CXCL1, CCL2, CCL3, CXCL8) at protein levels (29).…”

Novel Insights Into Gene Signatures and Their Correlation With Immune Infiltration of Peripheral Blood Mononuclear Cells in Behcet’s Disease

“…Through an intensive literature search in PubMed, we selected CCL4 as the central hub gene because of its known pathogenic role in autoimmune diseases including rheumatoid arthritis (RA) ( 31 ), multiple sclerosis (MS) ( 32 ) and Behcet’s disease ( 33 ). Accordingly, our patients were categorized into high- and low-expression groups of CCL4 for GSEA function and pathway analysis.…”

Behçet's syndrome: one year in review 2022

“…Finally, a study using 3' mRNA nextgeneration sequencing-based genomewide transcriptional profiling followed by analysis of differential expression signatures, Kyoto Encyclopedia of Genes and Genomes pathways, GO biological processes and transcription factor signatures highlighted the action of aberrant innate immune responses with a central role played by upregulated neutrophil chemotaxis. It did not support a major pathogenetic role for adaptive immunity-driven mechanisms (17).…”