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العنوان
Immunohistochemical Assessment of Phosphodiesterase 4A and Phosphodiesterase 4D in Relation to Serum Levels of Phosphodiesterase 4 in patients with chronic plaque psoriasis /
المؤلف
Abou El-Fadl, Dalia Abd El-Gawad.
هيئة الاعداد
باحث / داليا عبد الجواد ابو الفضل
مشرف / احمد ابراهيم رشيد
مشرف / مهيرة حمدى السيد
مشرف / نيرمين سامي عبد الفتاح
تاريخ النشر
2022.
عدد الصفحات
174 P. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الأمراض الجلدية
تاريخ الإجازة
1/1/2022
مكان الإجازة
جامعة عين شمس - كلية الطب - قسم الامراض الجلدية
الفهرس
Only 14 pages are availabe for public view

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from 174

Abstract

Findings and results of the present study have shown that:
 High significant increase in serum PDE4 level in psoriasis patients as compared to controls.
 High significant increase in immunohistochemical staining intensity of PDE4 A and PDE4 D in psoriasis patients in comparison to controls
 High significant increase in serum level of PDE4 and immunohistochemical staining of PDE4 A in relation to psoriasis severity as measured by PASI score.
 Highly significant positive correlation between serum PDE4 and PDE4 A score.
 No Significant correlation was found between immunohistochemical staining of PDE4 D and psoriasis severity as measured by PASI score.
 No significant correlation was found between serum PDE4 level and immunohistochemical staining of PDE4 D.
 No Significant relation between serum PDE4 level and immunohistochemical staining of PDE4 A and PDE4 D and duration of disease.
All of these finding are supporting the role of phosphodiesterase 4 in the pathogenesis of psoriasis.
RECOMMENDATIONS
F
urther studies are recommended on large scales of plaque psoriasis patients on the expression of PDE4 isoforms in skin in relation to the role of topical PDE4 therapy in treatment of psoriasis which hold promise and warrant further investigation.
It is also recommended to assess the site of expression of PDE4 B and PDE4 C in patients with plaque psoriasis in relation to controls (which wasn’t included in our study) for full detection of the exact sites of expression of PDE4 in skin which may increases our knowledge to best understand the exact role of PDE4 in the pathogenesis of psoriasis.

SUMMARY
P
soriasis is a chronic inflammatory, immune-mediated disease that predominantly affects the skin and joints. It is characterized by sharply demarcated, red, and scaly symmetrical plaques mainly on the elbow, knee or scalp.
The pathogenesis of psoriasis involves an interaction between genetic, environmental and immunological factors. The underlying pathomechanisms involve complex interaction between the innate and adaptive immune system. T cells interact with dendritic cells, macrophages, and keratinocytes, which can be mediated by their secreted cytokines. Dysregulation of the immune response is thought to result in a chronic imbalance in the production of pro-inflammatory and anti-inflammatory cytokines.
Cyclic adenosine monophosphate is a second messenger that plays a key role in the regulation of many biologic responses in humans, including inflammation, apoptosis, and lipid metabolism. PDEs consists of 11 isoenzymes (PDE1 to PDE11) and over 100 different isoforms that hydrolyse the phosphodiester bond in cyclic nucleotides and thus play a key role in regulating intracellular levels of the second messengers cAMP and cGMP responsible for multiple cellular metabolisms, and consequently regulating cell function. PDE-4 is an enzyme that mediates inflammatory responses and plays a role in psoriasis pathogenesis. There are four subtypes of PDE4, namely PDE4A–PDE4D, which are highly specific for cAMP degradation but not for cGMP.
The aim of the present study is to measure serum levels of PDE4 in patients with chronic plaque psoriasis and to assess possible correlation with PDE4 isoforms (A & D) in psoriatic skin in comparison to age and sex matched healthy controls.
The present study represents a case-control study which was carried out on 30 patients with chronic plaque psoriasis and 30 age and sex matched healthy volunteers as controls.
Each participant was subjected to a detailed history taking and careful clinical examination. Blood samples and skin punch biopsies were taken from all subjects to assess serum level of PDE4 by ELISA technique and IHC staining for PDE4-A and PDE4-D isoforms.
Results of the present study revealed: higher serum level of PDE4 in patients with chronic plaque psoriasis when compared with controls, and Immunohistochemical staining of PDE4 A in lesional skin is mainly expressed in peri-vascular lymphocytes with intensity ranging from faint to strong intensely positive, while immunohistochemical staining of PDE4 D in lesional skin is expressed mainly in epidermal basal cell layer with faint staining of dermis.
In conclusion, the results obtained in the present study indicates the role of PDE4 in the pathogenesis of psoriasis and eventually, the treatment with oral and topical PDE-4 inhibitors as promising therapies in the treatment armamentarium for plaque psoriasis.