TY - JOUR
TI - Distinct transcriptional profile of blood mononuclear cells in Behçet's disease: Insights into the central role of neutrophil chemotaxis
AU - Verrou, K.-M.
AU - Vlachogiannis, N.I.
AU - Ampatziadis-Michailidis, G.
AU - Moulos, P.
AU - Pavlopoulos, G.A.
AU - Hatzis, P.
AU - Kollias, G.
AU - Sfikakis, P.P.
JO - Rheumatology (United Kingdom)
PY - 2021
VL - 60
TODO - 10
SP - 4910-4919
PB - Oxford University Press
SN - null
TODO - 10.1093/rheumatology/keab052
TODO - alpha chemokine;  immunoglobulin enhancer binding protein;  messenger RNA;  transcription factor RelA;  transcription factor;  transcriptome, adult;  Article;  Behcet disease;  clinical article;  controlled study;  differential expression analysis;  down regulation;  female;  gene expression;  genetic profile;  genetic transcription;  genome analysis;  high throughput sequencing;  human;  human cell;  IL 1 signaling;  KEGG;  leukocyte;  male;  neutrophil chemotaxis;  NF kB signaling;  pathophysiology;  peripheral blood mononuclear cell;  protein fingerprinting;  TNF signaling;  transcriptome sequencing;  upregulation;  Behcet disease;  case control study;  gene expression regulation;  immunology;  metabolism;  middle aged;  mononuclear cell;  neutrophil;  pathology, Adult;  Behcet Syndrome;  Case-Control Studies;  Chemotaxis, Leukocyte;  Female;  Gene Expression Regulation;  High-Throughput Nucleotide Sequencing;  Humans;  Leukocytes, Mononuclear;  Male;  Middle Aged;  Neutrophils;  Transcription Factors;  Transcriptome
TODO - 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. © 2021 The Author(s) 2021.
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