Gene Expression Profiling in Behcet's Disease Indicates an Autoimmune Component in the Pathogenesis of the Disease and Opens New Avenues for Targeted Therapy

Antonio Puccetti, Piera Filomena Fiore, Andrea Pelosi, Elisa Tinazzi, Giuseppe Patuzzo, Giuseppe Argentino, Francesca Moretta, Claudio Lunardi, Marzia Dolcino

Research output: Contribution to journalArticle

Abstract

Behçet disease (BD) is a chronic inflammatory multisystem disease characterized by oral and genital ulcers, uveitis, and skin lesions. Disease etiopathogenesis is still unclear. We aim to elucidate some aspects of BD pathogenesis and to identify specific gene signatures in peripheral blood cells (PBCs) of patients with active disease using novel gene expression and network analysis. 179 genes were modulated in 10 PBCs of BD patients when compared to 10 healthy donors. Among differentially expressed genes the top enriched gene function was immune response, characterized by upregulation of Th17-related genes and type I interferon- (IFN-) inducible genes. Th17 polarization was confirmed by FACS analysis. The transcriptome identified gene classes (vascular damage, blood coagulation, and inflammation) involved in the pathogenesis of the typical features of BD. Following network analysis, the resulting interactome showed 5 highly connected regions (clusters) enriched in T and B cell activation pathways and 2 clusters enriched in type I IFN, JAK/STAT, and TLR signaling pathways, all implicated in autoimmune diseases. We report here the first combined analysis of the transcriptome and interactome in PBCs of BD patients in the active stage of disease. This approach generates useful insights in disease pathogenesis and suggests an autoimmune component in the origin of BD.

Original languageEnglish
Pages (from-to)4246965
Number of pages18
JournalJournal of Immunology Research
Volume2018
DOIs
Publication statusPublished - Apr 24 2018

Keywords

  • Autoimmunity/genetics
  • B-Lymphocytes/physiology
  • Behcet Syndrome/genetics
  • Blood Coagulation/genetics
  • Blood Vessels/physiology
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Inflammation/genetics
  • Interferon Type I/genetics
  • Janus Kinases/metabolism
  • Molecular Targeted Therapy
  • Protein Interaction Maps
  • STAT Transcription Factors/metabolism
  • Signal Transduction
  • Th17 Cells/physiology
  • Toll-Like Receptors/metabolism
  • Transcriptome/genetics

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