الفهرس 
PsoriasisOnly 14 pages are availabe for public view
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Abstract
P
soriasis is a relatively common chronic inflammatory disease, characterized by red, scaly, small to large plaques of diseased skin covered with silvery white scales, commonly affecting the scalp, trunk, elbows, knees and genital areas but can affect any part of the body including nails.
Our understanding of the pathogenetic events leading to psoriasis has improved significantly lately. It is well established that an interplay of environmental, genetic and immunological mechanisms is associated with the development of the disease.
The tissue reaction seen in it involves a complex immunological reaction of the skin with a severe inflammatory component and epidermal hyper-proliferation with abnormal keratinocyte differentiation. The immunopathogenesis of the disease is mainly T helper 1 (Th1) mediated, as it is characterized by increased activation of CD4+ T lymphocytes and systemic as well as local over expression of pro-inflammatory cytokines such as IL-2, IFN γ, IL-6 and TNF α.
Increasing attention has been focused on psoriatic keratinocytes which possess an enhanced ability to resist apoptosis compared with normal ones and this might be one of the key pathogenic mechanisms. The process of apoptosis is controlled by Bcl-2 family proteins including several pro-apoptotic e.g. Bax and anti-apoptotic proteins e.g. BID.
Apoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). Caspases cleave vital proteins, leading the cell to fragment into vesicles that are rapidly engulfed by phagocytes. Defects in apoptosis contribute in many diseases, ranging from cancer and autoimmunity to degenerative disorders. In mammalian cells, there are two pathways to apoptosis the ‘extrinsic’ pathway and the ‘intrinsic’ pathway each activating different initiator caspases (casepase-8 and casepase-9), but they converge at the level of effector caspases (casepase-3, 6 and 7).
Inhibitors of the apoptosis signaling pathway exist and play a major role in the apoptotic process. A key apoptosis regulatory protein of the Fas death pathway is cellular FLICE inhibitory protein (c-FLIP). FLIP has been shown to prevent the binding of procaspase-8 to FADD or interfering with the autocatalytic activation of caspase-8 at the death-inducing signaling complex leading to failure of initiation of the caspase cascade of the death receptor-mediated extrinsic apoptotic pathway.
Studies pinpointed that elevated c-FLIP expression protects cells from death receptor-mediated apoptosis, whereas down-regulation of c-FLIP sensitizes cells to death receptor-mediated apoptosis.
Twenty patients diagnosed clinically with psoriasis were enrolled in this study. All patients were subjected to full history taking, full clinical and dermatological examination and assessment of the degree of severity using PASI score and dividing the patients into mild, moderate and severe. A 2 mm punch biopsy was taken from each patient from lesional and non lesional areas (at least 1cm away from the lesion), all specimens were snap-frozen immediately in liquid nitrogen and stored at -80°C, followed by evaluation of c-FLIP mRNA gene expression using RT-PCR.
The level of c-FLIP protein was then correlated with gender, age, family history, age of onset of psoriasis, duration of the disease, preceding infection and severity of psoriasis. We established that there was direct significant relation between severity of psoriasis and c- FLIP protein levels measured.
The study also showed that the discrimination of the degree of severity of psoriasis by using psoriatic skin c-FLIP mRNA level can be reliable with 100% sensitivity, 81.2% specificity and 85% accuracy.