ASSESSMENT OF TRISTETRAPROLIN EXPRESSION IN LESIONAL SKIN OF PATIENTS WITH NON SEGMENTAL VITILIGO

Vitiligo is characterized by the selective loss of melanocytes, which in turn leads to totally amelanotic, non-scaly, chalky-white macule with distinct margins Vitiligo is the most common depigmenting skin disorder, with an estimated prevalence of 0.5-2% of the population in both adults and children worldwide Tumor necrosis factor (TNF-α), a pro-inflammatory cytokine is necessary for Th1 mediated response and immune homeostasis and the up-regulation of TNF-α can result in chronic inflammatory and autoimmune diseases . previous studies revealed a rise in transcript and protein levels of TNF-α in vitiligo patients The prime location of melanocytes, keratinocytes and fibroblasts is the epidermal microenvironment and these cells are capable of TNF-α expression and secretion TNF-α acts as an autocrine as well as a paracrine manner to suppress the melanocyte growth and proliferation ( Tristetraprolin (TTP) zinc finger protein 36 (ZFP36) is Ribonucleic acid (RNA) binding protein that preferentially binds to Adenylate-uridylate-rich (AU-rich) regions in the 3' untranslated regions (3'UTR) of target genes . Additionally, Tristetraprolin functions by destabilizing mRNAs encoding for oncogenes, cytokines (as TNFα), and chemokines involved in the inflammatory processes, by favoring their degradation and/or preventing their efficient translation The expression of proinflammatory mediator genes is tightly controlled by post-transcriptional regulation, which is mediated by a set of immune-related RNA binding proteins, such as tristetraprolin, Roquin, and Regnase

Tristetraprolin (TTP) zinc finger protein 36 (ZFP36) is Ribonucleic acid (RNA) binding protein that preferentially binds to Adenylate-uridylate-rich (AU-rich) regions in the 3' untranslated regions (3'UTR) of target genes (Brooks et al., 2013). Additionally, Tristetraprolin functions by destabilizing mRNAs encoding for oncogenes, cytokines (as TNFα), and chemokines involved in the inflammatory processes, by favoring their degradation and/or preventing their efficient translation

Inclusion Criteria: This study will include adult patients>18 yrs with non -segmental vitiligo attending the dermatology outpatient clinics at Sohag University, Egypt. A group of participants will be included as a control group.This control group will be taken from patients seeking for abdominoplasty in plastic surgery department at Sohag University Hospital. Exclusion Criteria: - 1)Pregnancy. 2)Patients with chronic inflammatory skin disorders. 3)Patients on antioxidants or anti-inflammatory drugs. 4)Patients on topical or systemic treatment for vitiligo in the last 4 weeks prior to enrollment in the study. 5)Patients with other autoimmune diseases as thyroiditis. lupus erythematosus and rheumatoid arthritis 6)Patients with diabetes mellitus (DM).

Alghamdi KM, Khurrum H, Taieb A, Ezzedine K. Treatment of generalized vitiligo with anti-TNF-alpha Agents. J Drugs Dermatol. 2012 Apr;11(4):534-9.

Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011 Sep;65(3):473-491. doi: 10.1016/j.jaad.2010.11.061.

Alkhateeb A, Fain PR, Thody A, Bennett DC, Spritz RA. Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Pigment Cell Res. 2003 Jun;16(3):208-14. doi: 10.1034/j.1600-0749.2003.00032.x.

Brooks SA, Blackshear PJ. Tristetraprolin (TTP): interactions with mRNA and proteins, and current thoughts on mechanisms of action. Biochim Biophys Acta. 2013 Jun-Jul;1829(6-7):666-79. doi: 10.1016/j.bbagrm.2013.02.003. Epub 2013 Feb 18.