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 Behçet'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, Kyoto Encyclopedia of Genes and Genomes pathways, GO biological processes and transcription factor signatures. RESULTS: Differential expression analysis clustered the transcriptomes of 13 patients and one healthy subject separately 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 upregulated and downregulated, respectively, in BD vs controls by at least 2-fold. The most upregulated genes comprised an abundance of CC- and CXC-chemokines. Remarkably, the 5 out of top 10 upregulated biological processes involved leucocyte recruitment to peripheral tissues, especially for neutrophils. Moreover, NF-kB, TNF and IL-1 signalling 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 peripheral blood mononuclear cells derived from patients with BD does not support a major pathogenetic role for adaptive immunity-driven mechanisms, but clearly points to the action of aberrant innate immune responses with a central role played by upregulated neutrophil chemotaxis.

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