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العنوان
Detection of possible role of CD11a in pathogenesis of primary immune thrombocytopenia and effect of immunosuppressive therapy on its level /
المؤلف
Mostafa, Mona Ibrahim.
هيئة الاعداد
باحث / مني إبراهيم مصطفي جعيدي
مشرف / هويدا عبد الحكيم نفادي
مناقش / أحمد محمد علي عبيد الله
مناقش / أسامة أحمد إبراهيم
الموضوع
Thrombocytopenia.
تاريخ النشر
2021.
عدد الصفحات
104 p. ;
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
أمراض الدم
الناشر
تاريخ الإجازة
13/12/2020
مكان الإجازة
جامعة أسيوط - كلية الطب - Internal Medicine Department
الفهرس
Only 14 pages are availabe for public view

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from 114

Abstract

ITP is one of auto immune diseases that affecting relatively young individual and may need long term therapy, although many lines of treatment for ITP are discovered including corticosteroids and intravenous immunoglobulin as the first line choice, and many drugs including rituximab have also been tried as second-line treatments However, the curative effect is unsatisfactory. Although auto reactive B lymphocytes secreting antiplatelet antibodies are considered as the main defect, substantial evidence suggests that a generalized dysfunction of auto reactive T cells is the critical immunopathological cause of ITP and the antiplatelet autoantibodies are under the control of T cells and the cytokines they produce. Lymphocyte function associated antigen-1 (LFA-1) belonging to the integrin family is composed of the alpha chain CD11a and beta chain CD18 heterologous dimers, The combination of LFA-1 and ICAM-1 can provide coordinated stimulus signal and promote lymphocyte activation, proliferation and differentiation, The expression of ICAM-1 and LFA-1 is significantly higher on lymphoid cells and vascular endothelial cells in rheumatoid arthritis (RA), indicating that the combination of LFA-1 and ICAM-1 may play an important role in the progression of RA. An LFA-1 antagonist that blocks binding of ICAM-1 to LFA-1, has recently been approved in the United States for the treatment of signs and symptoms of DED (one of autoimmune disease). In our study we tried to detect the possible role of LFA-1/ ICAM-1 in pathogenesis of ITP and this will enable us to use blockers to this combination as new line of treatment in primary ITP patients and some of them reach clinical trials. This work is case control type included 40 newly diagnosed ITP patients, who were admitted to Clinical Haematology Unit, Assiut University Hospital from December 2017 to Oct 2019 , 40 patients newly diagnosed as primary ITP were assessed clinically, and laboratory parameters were obtained at baseline visit and at 6-month after treatment by immunosuppressive therapy , ITP bleeding scores was assessed at baseline visit for all recruited patients and 40 healthy controls were included in this study to compare means of level of CD11a which expressed on B and T lymphocytes between patients and control. There is high statistically significant difference between cases and control in the level of CD11a in CD3+ cells (p value=0.000) with more expression in patients than control and highly significant difference in CD19+ cells (p value= 0.001) with more expression in patients than control while there is no significant difference in the level of CD11a in CD4+ cells between patients and control (p value = 0.19), so In this study it is proved that the expression of CD11a on B and T lymphocytes are excess in patients with primary ITP than healthy control individuals which reflect possible role of LFA-1/ ICAM-1 in pathogenesis of ITP. There is no significant correlation between level of CD11a in CD3+ and CD19+ and platelet count (p value = 0.6 and 0.5 respectively) and bleeding score(p =0.79 and 0.71 respectively) this means that the level of CD11a expression not reflect the severity of the disease at presentation either by platelet count nor by severity of bleeding All patients in the study received immunosuppressive therapy and there was no statistically significant difference in the MFI of CD11a in CD19+ cells between patients who responded and not responded to therapy (p=0.50) while There was high statistically significant difference in the MFI of CD11a in CD3+ cells between patients who responded and not responded to therapy (p=0.000) with higher level in patients who showed resistance to therapy this provide to us an impression that the excessive expression of CD11a in T-lymphocytes in patients of ITP may be a cause of resistance to immunosuppressive therapy and other studies to determine the cutoff point of CD11a in T-lymphocytes at which we can suspect resistance to immunosuppressive are recommended Also there was no statistically significant difference in the means of level of CD11a in CD3+ and CD19+ cells between patients before and after response to treatment with p value = 0.19 and 0.16 respectively so adding treatment agent that block LFA-1/ ICAM-1 interaction may provide a new treatment line in ITP patient. Further studies are recommended with larger sample size to confirm the theory that LFA-1/ICAM-1 binding has role in pathogenesis of primary ITP. And further studies are recommended to detect effect of other kinds of immunosuppressive drugs alone on the level of CD11a.