الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Psoriasis is a common chronic inflammatory skin disease characterized by marked thickening of the epidermis, tortuous and dilated dermal blood vessels, and characteristic inflammatory cell infiltrates. Although the pathogenesis of psoriasis has not been fully elucidated, tumor necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) are over-expressed in psoriasis and are believed to have central roles in its processes. In particular, biological agents targeting TNF-α signaling are highly effective in the treatment of patients with psoriasis. Progranulin (PGRN) – also known as granulin epithelin precursor, pro-epithelin and acrogranin – is a 576-amino-acid autocrine growth factor with multiple physiological and pathological functions. PGRN plays a critical role in early embryogenesis, wound healing, tumorigenesis, maintenance of neuronal survival, host defense and inflammation. PGRN was a ligand of TNF receptors (TNFR). PGRN blocks TNF-α-mediated signaling pathways by competing with TNF-α binding to TNFR1/2 and exhibits anti-inflammatory function in inflammatory arthritis models. Progranulin has been increasingly the focus of research on autoimmune diseases because of its anti-inflammatory effect. In contrast to its anti-inflammatory role, PGRN also has proinflammatory effects in obesity and insulin-resistant diabetes through the production of IL-6. Hence, the exact function of PGRN may vary depending on the pathophysiological context of the disease. In the current study, we aimed to study relationship between serum progranulin/tumor necrosis factor- α and psoriasis vulgaris activity. In the current study, we found that there was significant increase in PGRN level in cases versus control (p.value <0.001). In the current study, we found that there was significant increase in TNF-α level in cases versus control (p.value <0.001). In the current study, we found that that there was significant decrease in PGRN/TNF-α ratio in cases versus control (p.value< 0.001). In the current study, we found that the mean PASI in cases groups was 15.8 and most of cases were moderate degree 68.6%, severe in 17.1% and mild in 14.3%. In the current study, we found that there were significant differences between PASI degree and PGRN level. There were significant differences between PASI degree and TNF-α level. In the current study, we found that there were significant differences between PASI degree and PGRN/TNF-α ratio. There was negative significant correlation between PASI and PGRN/TNF-α ratio. PGRN/TNF-α ratio at cutoff ≤6.8 with sensitivity, specificity, PPV, NPV, AUC, P 100%, 90 %, 92.1%, 100 %, 94%, <0.001 respectively, TNF-α level at cutoff >4.2 with sensitivity, specificity, PPV, NPV 100% all and AUC, P 1,<0.001, PGRN level at cutoff >40 with sensitivity, specificity, PPV, NPV, AUC, P 94.29%, 93.33%, 94.3%, 93.3%, 98%, <0.001 respectively. The administration of recombinant human PGRN or a recombinant PGRN derivative named Atsttrin consisting of three modified granulin motifs and their accompanying linker regions, had strong anti-inflammatory effects. PGRN and its derivative Atsttrin may represent a promising therapeutic agent in the treatment of rheumatoid arthritis and contact dermatitis. Some studies speculate potential applications of PGRN and Atsttrin in other autoimmune diseases, such as psoriasis and inflammatory bowel disease, on the grounds that TNF inhibitors have been used for treating such diseases.