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العنوان
Immunohistochemical Expression of Discoidin Domain Receptor1 (DDR1) in Psoriasis /
المؤلف
Elkadi , Walaa Sabry Mahmoud .
هيئة الاعداد
باحث / ولاء صبرى محمود القاضى
مشرف / محمد أحمد باشا
مشرف / رحاب منير سمكه
مناقش / محمد عبد الواحد جابر
مناقش / السيد شعبان هويدي
الموضوع
psoriasis.
تاريخ النشر
2022.
عدد الصفحات
92 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب التناسلي
تاريخ الإجازة
24/3/2022
مكان الإجازة
جامعة المنوفية - كلية الطب - الامراض الجلدية والتناسلية
الفهرس
Only 14 pages are availabe for public view

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Abstract

Psoriasis is a chronic inflammatory skin disorder involving both innate and adaptive immunity processes.
Discoidin domain receptors (DDRs); DDR1 and DDR2, lie at the intersection of two large receptor families, namely the extracellular matrix and tyrosine kinase receptors. DDR1 promotes inflammation in atherosclerosis, lung fibrosis and kidney injury, while DDR2 contributes to osteoarthritis. As such, DDRs are uniquely positioned to function as sensors for extracellular matrix and to regulate a wide range of cell functions from migration and proliferation to cytokine secretion and extracellular matrix homeostasis/ remodeling. While activation of DDRs by extracellular matrix collagens is required for normal development and tissue homeostasis, aberrant activation of these receptors following injury or in disease is detrimental.
There was a few previous reports study the relationship between immunohistochemical expression of DDR1 and psoriasis. But until now, this relationship is not clearly defined.
This study aimed to investigate the role of DDR1 in pathogenesis of psoriasis through its immunohistochemical expression in involved and uninvolved skin in psoriasis and to correlate its expression with the clinical and histopathological parameters.
This case control study was conducted on total number of 60 subjects. Divided into 2 groups: group 1: 40 patients with psoriasis vulgaris as patient group, and group 2: 20 age and gender matched healthy volunteers as a control group. Cases was selected from the Dermatology Outpatient Clinic at Menoufia University Hospital.The pathological examination of study was done at Pathology Department, Menoufia University.
All included patients were subjected to complete history taking and clinical examination, Immunohistochemical staining was performed using rabbit polyclonal IgG antibody (DDR1);
The cases included 18 females (45%) and 22 males (55%). The age of the selected cases ranged between 15 and 75 years with a mean age 42.20±18.36 years. There was no significant difference between case group and control group regarding age and gender.
There were 16 (40%) positive smokers in the studied cases. Regarding comorbidities, 2 (25%) of the patients suffered from hypertension, 4 (50%) were diabetic, 2 (25%) were having rheumatoid arthritis. Family history existed in 13 (32.5%).
The age of onset of the patient disease was 36.05 ± 18.35 years with average duration of the disease of 4.80 ± 5.34 years. The disease was described as stationary in 13 (32.5%) of the patients and 27 (67.5%) were described as progressive. PASI score was described as mild in 25 (62.5%), moderate in 13 (32.5%) and severe in 2 (5%) of the patients. The average PASI score reported was 12.17 ± 9.6.
On comparing histopathological data of lesional and perilesional psoriatic skin; There were highly significant differences between lesional and perilesional skin regarding presence of acanthosis and its degree, psoriasiform hyperplasia, hyperkeratosis, parakeratosis, suprapapillary thining, granular cell layer, spongiosis, tips of rete ridges and presence of exocytosis and type of exocytosis (P<0.001) for all. Significant
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differences regarding degree of psoriasiform hyperplasia, degree of hyperkeratosis and degree of suprapapillary thining (P=0.001, 0.001and 0.006 respectively).
On comparing between lesional and perilesional according to dermal changes; There were highly significant differences between leisional and perilesional skin regarding to elongation of papillary dermis, degree of papillary edema, dilation of blood vessel and its degree, tortuosity of blood vessel and its degree, degree of infiltrate and its type (P<0.001) for all. Significant differences regarding elongation of papillary dermis, papillary edema, and dermal fibrosis (P=0.027, 0.045 and 0.025 respectively).
Regarding epidermal DDR1 expression; There were highly significant differences between the studied groups regarding H score and its category (P<0.001). In normal skin; DDR 1 was positively expressed in all control skin sections both in epidermis and dermis. Regarding categories of H score of DDR 1 expression, low H score was present in all sections. While H score ranged from 30 – 80 with mean ±SD of 57.0 ± 15.59. In perilesional skin epidermis; DDR 1 was positively expressed in all perilesional skin epidermis. Pattern was cytoplasmic in all cases. Regarding intensity, mild expression was present in 10% of the sections and 90% had strong expression. Regarding categories of H score of DDR 1 expression, low H score was present in 67.5% of the sections, high H score was present in 32.5% of the cases. While H score ranged from 80 -130 with mean ±SD of 94.25 ± 20.99. In lesional skin epidermis; DDR 1 was positively expressed in all lesional skin epidermis. Pattern was cytoplasmic in all cases. Regarding intensity, strong expression was present in all sections. Regarding categories of H score of DDR 1 expression, low H score was present in 17.5% of the sections, high H score was present in 82.5% of the cases. While H score ranged from 190 -250 with mean ±SD of 234 ± 22.51.
Regarding dermis DDR1 expression; There were highly significant difference between the studied groups regarding H score category and intensity of staining (P<0.001) for both. . In normal skin; DDR 1 was positively expressed in all sections. Regarding categories of H score of DDR 1 expression, low H score was present in all sections. While H score ranged from 30 – 120 with mean ±SD of 89.5 ± 28.19. In perilesional skin dermis; DDR 1 was positively expressed in all perilesional skin epidermis. Pattern was cytoplasmic in all cases. Regarding intensity, mild expression was present in 37.5% of the sections, 25% had moderate expression and 37.5% had strong expression. Regarding categories of H score of DDR 1 expression, low H score was present in 52.5% of the sections, and high H score was present in 47.5% of the cases. While H score ranged from 90 -130 with mean ±SD of 106 ± 195. In Lesional skin dermis; DDR 1 was positively expressed in all perilesional skin epidermis. Pattern was cytoplasmic in all cases. Regarding intensity, strong expression was present in 50% of the sections, 35% were having moderate intensity, and 15% were having mild intensity. Regarding categories of H score of DDR 1 expression, low H score was present in 47.5% of sections, and high H score was present in 52.5% of the cases. While H score ranged from 30 -200 with mean ±SD of 109 ± 65.74.
Regarding to the relation between lesional epidermal and dermal DDR1 H score with demographic and clinical data; a highly significant relationship was found between epidermal DDR1 H score and gender (P=0.001), Whereas overexpression of DDR1 was significantly related to male gender. Regarding smoking, a significant relationship was detected between epidermal and dermal DDR1 H score and smoking (P0.034 and 0.009)
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respectively. A significant relationship was noted between dermal DDR1 and medical diseases and its type (P=0.043 for both). A significant relationship was detected between epidermal DDR1 and family history (P=0.014). A significant relationship was noted between epidermal and dermal DDR1 H score and PASI score (P=0.049 and 0.003) respectively.
There was a significant negative correlation between DDR1 epidermal H score and PASI score (r =-0.318 and P =0.045). There was a significant positive correlation between DDR1 dermal H score and age (r=0.500 and P=0.001). There was a significant positive correlation between DDR1 dermal H score and age of onset (r =0.667 and P<0.001). There was a significant negative correlation between DDR1 dermal H score and duration of disease (r =-0.477 and P =0.002). There was a significant negative correlation between DDR1 dermal H score and PASI score (r=-0.683 and P<0.001).
Regarding to the relation between epidermal DDR1 H score category with demographic and clinical data, a significant relationship was noted between epidermal DDR1 H score category and gender (P =0.033), whereas 63.6% of high category were male and 85.7% of low category were female. A significant relationship was noted between epidermal DDR1 H score category and medical disease (P =0.205). Whereas 87.9% of high category had no associated diseases and 57.1% of low category had associated diseases. A significant relationship was noted between epidermal DDR1 H score category and PASI score category (P =0.013), whereas 69.7% of high category were mild and 28.6% of low category were mild.
Regarding to the relation between lesional dermal DDR1 H score category with demographic and clinical data, a significant relationship was noted between dermal H score and gender (P = 0.0028), whereas 71.4% of high category were male and 63.2% of low category were females. A highly significant relationship was detected between dermal H score and age (P < 0.001), whereas DDR1overexpression was associated with old age. A highly significant relationship was found between dermal H score and smoking (P =0.003), whereas 61.9% of high category were smokers. A highly significant relationship was noted between dermal H score and age of onset (P < 0.001), whereas DDR1overexpression was associated with older age of onset. A significant relationship was noted between dermal H score and duration of the disease (P=0.019), whereas DDR1overexpression was associated with long duration. A significant relationship was noted between dermal H score and PASI score and its category (P<0.001) for both, whereas DDR1overexpression was associated with lower value. A significant relationship was detected between dermal H score and PASI score category (P=0.004), whereas DDR1overexpression was associated with lower value.
Regarding the relation between lesional epidermal DDR1 H score with epidermal changes. A significant relationship was noted between epidermal H score of DDR1 and degree of parakeratosis (P=0.039), whereas DDR1overexpression was associated with mild degree of parakeratosis. A significant relationship was detected between epidermal H score of DDR1 and Munro microabscess (P =0.031), whereas DDR1 overexpression was associated with absence Munro microabscess.
Regarding to the relation between lesional dermal DDR1 H score with dermal changes, a significant relationship was noted between dermal DDR1 H score with papillary edema (P<0.001), whereas DDR1overexpression was associated with the presence of edema. A significant relationship was noted between dermal DDR1 H score with dermal fibrosis (P =0.008), whereas DDR1 overexpression was associated with the absence of dermal fibrosis.