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

• DOI: 10.1155/2018/4246965
• Publication Date: 2018-04-24T19:32:32Z
• Authors: Antonio Puccetti; Piera Filomena Fiore; Andrea Pelosi; Elisa Tinazzi; Giuseppe Patuzzo; Giuseppe Argentino; Francesca Moretta; Claudio Lunardi; Marzia Dolcino
• Keywords: Behcet disease, Gene expression profiling, transcriptome, IL17, autoimmunity; Autoimmunity; 03 medical and health sciences; 0302 clinical medicine; Gene Regulatory Networks; Molecular Targeted Therapy; Protein Interaction Maps; Blood Coagulation; Janus Kinases; Inflammation; B-Lymphocytes; Behcet Syndrome; Gene Expression Profiling; Toll-Like Receptors; RC581-607; 3. Good health; STAT Transcription Factors; Interferon Type I; Blood Vessels; Th17 Cells; Immunologic diseases. Allergy; Transcriptome; Research Article; Signal Transduction

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.