Analysis of Transcriptomic and Proteomic Data in Immune-Mediated Diseases

Abstract

Psoriasis (a skin disease) and Crohn’s disease (a disease of the intestinal epithelium) are multifactorial diseases caused by abnormalities in genetic machinery regulation. Both pathologies disturb the immune system, and the pathological processes are triggered by environmental factors. In the case of psoriasis, these factors are psychoemotional stresses, infections (group A streptococci and Staphylococcus aureus), drugs (lithium-containing, antimalarial, and antituberculous agents and Novocain), smoking, and mechanical damages (the so-called Koebner phenomenon) [Bowcock A et al., 2004]. Psoriasis vulgaris is one of the most prevalent chronic inflammatory skin diseases affecting approximately 2% of individuals in Western societies, and found worldwide in all populations. Psoriasis is a complex disease affecting cellular, gene and protein levels and presented as skin lesions. The skin lesions are characterized by abnormal keratinocyte differentiation, hyperproliferation of keratinocytes, and infiltration of inflammatory cells [Boehncke WH et al. 1996; Ortonne JP, 1996]. The factors triggering Crohn’s disease include psychoemotional stresses, infections (Mycobacterium avium ssp. paratuberculosis and invasive Escherichia coli variants), drugs (antibiotics and nonsteroid antiimflammatory agents), smoking, and nutritional regimen [Sartor R., 2006]. Crohn’s disease known only since the 1920s [Crohn B et al., 1932] and now affecting up to 0.15% of the northwest European and North American population [Binder V., 2005]. Both psoriasis and Crohn’s disease are now regarded as incurable, and the goal of their therapy is to extend the remission periods and decrease the severity of the disease. These two diseases are tightly related at the genetic level, as over five genetic loci are involved in the development of both psoriasis and Crohn’s disease. The mechanisms of both psoriasis and Crohn’s disease are complex and involve genetic and environmental factors. As we gain more knowledge about molecular pathways implicated in diseases, novel therapies emerge (such as etanercept and infliximab that target TNF-α or CD11amediated pathways [Pastore S et al., 2008; Gisondi P et al., 2007]). We have studied earlier the components of AP-1 transcription factor as psoriasis candidate genes. This study was performed by bioinformatics analysis of the transcription data using the GEO DataSets database (http://www.ncbi.nlm.nih.gov/geo/) [Piruzian ES et al., 2007].