摘要:
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.
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