Bioinformatics analysis reveals transcriptome and microRNA signatures and drug repositioning targets for IBD and other autoimmune diseases

Background: Inflammatory bowel disease (IBD) is a complex disorder involving pathogen infection, host immune response, and altered enterocyte physiology. Incidences of IBD are increasing at an alarming rate in developed countries, warranting a detailed molecular portrait of IBD. Methods: We used large‐scale data, bioinformatics tools, and high‐throughput computations to obtain gene and microRNA signatures for Crohn's disease (CD) and ulcerative colitis (UC). These signatures were then integrated with systemic literature review to draw a comprehensive portrait of IBD in relation to autoimmune diseases. Results: The top upregulated genes in IBD are associated with diabetogenesis (REG1A, REG1B), bacterial signals (TLRs, NLRs), innate immunity (DEFA6, IDO1, EXOSC1), inflammation (CXCLs), and matrix degradation (MMPs). The downregulated genes coded tight junction proteins (CLDN8), solute transporters (SLCs), and adhesion proteins. Genes highly expressed in UC compared to CD included antiinflammatory ANXA1, transporter ABCA12, T‐cell activator HSH2D, and immunoglobulin IGHV4–34. Compromised metabolisms for processing of drugs, nitrogen, androgen and estrogen, and lipids in IBD correlated with an increase in specific microRNA. Highly expressed IBD genes constituted targets of drugs used in gastrointestinal cancers, viral infections, and autoimmunity disorders such as rheumatoid arthritis and asthma. Conclusions: This study presents a clinically relevant gene‐level portrait of IBD subtypes and their connectivity to autoimmune diseases. The study identified candidates for repositioning of existing drugs to manage IBD. Integration of mice and human data point to an altered B‐cell response as a cause for upregulation of genes in IBD involved in other aspects of immune defense such as interferon‐inducible responses. (Inflamm Bowel Dis 2012;)

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