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العنوان
Evaluation of regulatory T cells among steroid free live-donor kidney transplant recipients /
المؤلف
El-Mowafy, Ahmed Yahia Bedir.
هيئة الاعداد
باحث / أحمد يحيى بدير الموافى
مشرف / محمد عبدالقادر صبح
مشرف / سمير توفيق صلى
مشرف / أمانى مصطفى اسماعيل
مناقش / غاده محمد القنيشى
مناقش / صالح سعيد نجا
الموضوع
Kidney Transplantation. Regulatory t cells. Oncology. Internal Medicine.
تاريخ النشر
2022.
عدد الصفحات
online resource (176 pages) :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الطب الباطني
تاريخ الإجازة
1/1/2021
مكان الإجازة
جامعة المنصورة - كلية الطب - قسم امراض الباطنه العامه
الفهرس
Only 14 pages are availabe for public view

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from 176

Abstract

Background Corticosteroids are considered the backbone of most used immunosuppressive protocols in kidney transplantation (Suszynski., 2013). Steroid-avoidance immunosuppressive regimens have been used widely in different centers worldwide. The results are promising and support the safety and efficacy of these regimens even if the patient is at high risk (Aull et al., 2012). Transplant tolerance has been defined as maintenance of stable allograft function in the absence of immunosuppressive therapy. Regulatory T cells (Treg) play a key role in the generation and maintenance of immune tolerance (Braza et al., 2015). Several key immunologic findings led to the major effort to induce tolerance by ablation of the mature immune system to allow the establishment of chimerism by transfer of donor bone marrow or lymphoid cells. In adults, ablation of the immune system has been achieved by whole-body irradiation, total lymphoid irradiation, myeloablation by cytotoxic agents, selective T-cell depletion by monoclonal antibodies, or antilymphocyte globulin, which all has led to successful transplant outcomes (Scandling et al., 2008). Tregs are defined as those anergic and hyporesponsive to stimulation of T-cell receptor (TCR) with suppressive action on the proliferation and activation of helper CD4+ T cells and cytotoxic CD8+ T cells via cell-to-cell contact. Regulatory t cells with their Foxp3-expressing marker are strongly suppressive of proliferation of effector T cells and memory T cells, thus controlling excess immune response to foreign antigens, and maintain self-tolerance. Patients and Methods : This retrospective cohort study was held in Urology and Nephrology Center, Mansoura University, Egypt in the duration between 10/2019 and 10/2021 under protocol No.MDP.19.01.133. The study included 100 low immunologic-risk kidney transplant recipients who received kidney transplantation in the center between January/2012 and December/2015. The included patients were divided into 2 groups: Study group: 50 kidney transplant recipients were maintained on steroid-free immunosuppressive regimen (tacrolimus -Tac-, mycophenolate mofetil -MMF). Control group: 50 kidney transplant recipients received steroids (St) as a part of their immunosuppressive regimen (steroid, tacrolimus, mycophenolate mofetil). They were matched in age, sex and date of transplantation. Control group received steroids in spite of their low immunologic-risk due to either their original kidney disease (OKD) of high risk of recurrence or being enrolled in other studies. Results : Both groups were comparable regarding demographics and baseline medical conditions. Also, the majority of our cohort had 2 mismatched alleles in HLA class I and 1 mismatched alleles in HLA class II with higher frequency among steroid-free group (p value: 0.025). All patients in both groups had negative donor-specific anti-bodies either before transplantation or at time of enrollment in the study. However, 4 patients had donor non-specific anti-HLA antibodies less than 10% before transplantation in steroid-based group and 2 patients in steroid-free group with no statistically significant difference. Both groups were comparable regarding blood transfusion before transplantation. Ischemia time ranged from 25 minutes to 68 minutes in the total cohort with no statistical significant difference between both groups. Delayed graft function occurred among 4 patients out of 50 in steroid-free group with statistically significant difference (p value: 0.04). There was no statistically significant difference between both groups regarding induction therapy Steroid-free patients received higher steroid doses before withdrawal of steroids (p value: 0.0001). On comparison between steroid-free group and steroid-based group, CD4+ cells, CD8+cells and CD4+CD25highCD127low cells expression was comparable 5 years after transplantation. Also, CD4/CD8 ratio was comparable. Risk factors for rejection were included through 5 steps in the multivariate analysis to detect risk factors for rejection among our cohort and relation of CD4, CD8 and CD4+CD25highCD127low cell percentage to incidence of rejection. Related donation was associated with lower incidence of rejection (OR: 0.05, p value: 0.006). Delayed graft function and acute tubular necrosis was associated with increased risk of rejection (OR: 7.3, p value: 0.04). CD8 percent had positive correlation to risk of incidence of rejection (p value: 0.015). Conclusion : Long- term immune tolerance state could be achieved successfully among steroid-free kidney transplant recipients after induction with basiliximab with comparable rejection rates as steroid avoidance did not affect negatively the expression of CD4+CD25+CD127- regulatory t-cells. Regulatory t-cells down regulated cytotoxic CD8+ cells successfully among steroid avoidance kidney transplant recipients. CD4+CD25+CD127- regulatory t-cells expression is not a marker for rejection. However, CD8+ cells expression could be used as a marker for rejection.