终末分化效应cd8 + t淋巴细胞在无创肝移植排斥诊断中的应用

S. Korotkov, V. Smolnikova, V. Hrynevich, O. Lebed, M. N. Vasilenka, D. Efimov, A. Fedoruk, A. Shcherba, S. I. Kryvenka, O. Rummo, Minsk Scientifc, Minsk Belarus Hematology, Minsk Belarus City Clinical Pathologoanatomic Bureau
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There was carried out a single center observational retrospective case-control pilot study, including 45 recipients after orthotopic liver transplantation. According to the postoperative clinical course the patients were stratifed into 2 groups depending on the presence of graft rejection episodes. All patients got immunosuppressive therapy after liver transplantation. Immunophenotypes of the recipients were determined by flow cytometry method. Percutaneous liver graft biopsy was performed in all patients, the results of histological examination were evaluated according to the international Banff schema for grading liver allograft rejection. Results. The results of liver biopsies showed that 14 (31%) out of 45 patients had morphological signs of rejection. The patients with rejection had a reliably higher level of CD8+ Temra cells absolute number (0,23 (0,14;0,38) x 109/l) in comparison to those without rejection (0,09) (0,034;0,16) x 109/l (p=0,034)). The results of ROC-analysis have shown that the most optimal cut-off threshold of CD8+ T-lymphocytes level in immune-mediated graft dysfunction diagnostics in the late post-transplant period is 0,1882x109/l; sensitivity and specifcity in this case being 73,33 (95%; 44,9-92,0) and 96,55 (95%; 82,2-99,4) respectively. Conclusions. The increase of terminally differentiated effector CD8+ T-lymphocytes absolute number has diagnostic importance in patients with immune-mediated graft dysfunction in the late post-transplant period. High sensitivity and specifcity of cut-off threshold of CD8+ Temra lymphocytes absolute number in patients after liver transplantation as well as reliable difference between cell number in patients with normal postoperative period and in patients with immune-mediated graft dysfunction allow considering T-lymphocyte subpopulation as a rejection predictor in the late post-transplant period. 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引用次数: 0

摘要

背景。免疫介导的移植物功能障碍的患病率为40%,是现代移植学的主要问题之一。虽然经皮肝移植活检与2.2%的病例发生的不同并发症有关,但也可能导致致命的结果。目的:建立一种利用终末分化效应CD8+ t淋巴细胞诊断移植后晚期移植物功能障碍的无创方法。材料和方法。进行了一项单中心观察性回顾性病例对照先导研究,包括45例原位肝移植受者。根据术后临床病程,根据患者是否出现排斥反应分为两组。所有患者在肝移植后均接受免疫抑制治疗。流式细胞术检测受体免疫表型。所有患者均行经皮肝移植活检,组织学检查结果按照国际同种异体肝移植排斥反应分级Banff模式进行评估。结果。肝活检结果显示,45例患者中有14例(31%)出现排斥的形态学征象。排斥反应患者的CD8+ Temra细胞绝对数量(0,23 (0,14;0,38)× 109/l)比无排斥反应患者(0,09)(0,034;0,16)× 109/l (p=0,034))可靠地更高。roc分析结果显示,移植后晚期免疫介导的移植物功能障碍诊断中CD8+ t淋巴细胞水平的最佳截止阈值为0.1882 × 109/l;本病例的敏感性和特异性为73,33 (95%;44,9-92,0)和96,55 (95%;82年,2 - 99,分别4)。结论。终末分化效应CD8+ t淋巴细胞绝对数量的增加对移植后晚期免疫介导的移植物功能障碍患者具有诊断意义。肝移植患者CD8+ Temra淋巴细胞绝对数量的截止阈值的高敏感性和特异性,以及正常术后患者和免疫介导的移植物功能障碍患者细胞数量的可靠差异,允许将t淋巴细胞亚群作为移植后晚期排斥反应的预测因子。CD8 + t淋巴球绝对数量之间的相关性和组织学检查结果使前一个替代,更重要的是,安全的方法在肝移植排斥的早期诊断。
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THE OPPORTUNITIES OF NON-INVASIVE LIVER GRAFT REJECTION DIAGNOSTICS BY USING TERMINALLY DIFFERENTIATED EFFECTOR CD8+ T-LYMPHOCYTES
Background. Immune-mediated graft dysfunction with the prevalence of 40% is one of the main problems of modern transplantology. Although percutaneous liver graft biopsy is associated with the development of different complications occurring in 2,2% of cases and can also lead to fatal outcome. Objective – to develop a noninvasive method of graft dysfunction diagnostics in the late post-transplant period using terminally differentiated effector CD8+ T-lymphocytes. Material and methods. There was carried out a single center observational retrospective case-control pilot study, including 45 recipients after orthotopic liver transplantation. According to the postoperative clinical course the patients were stratifed into 2 groups depending on the presence of graft rejection episodes. All patients got immunosuppressive therapy after liver transplantation. Immunophenotypes of the recipients were determined by flow cytometry method. Percutaneous liver graft biopsy was performed in all patients, the results of histological examination were evaluated according to the international Banff schema for grading liver allograft rejection. Results. The results of liver biopsies showed that 14 (31%) out of 45 patients had morphological signs of rejection. The patients with rejection had a reliably higher level of CD8+ Temra cells absolute number (0,23 (0,14;0,38) x 109/l) in comparison to those without rejection (0,09) (0,034;0,16) x 109/l (p=0,034)). The results of ROC-analysis have shown that the most optimal cut-off threshold of CD8+ T-lymphocytes level in immune-mediated graft dysfunction diagnostics in the late post-transplant period is 0,1882x109/l; sensitivity and specifcity in this case being 73,33 (95%; 44,9-92,0) and 96,55 (95%; 82,2-99,4) respectively. Conclusions. The increase of terminally differentiated effector CD8+ T-lymphocytes absolute number has diagnostic importance in patients with immune-mediated graft dysfunction in the late post-transplant period. High sensitivity and specifcity of cut-off threshold of CD8+ Temra lymphocytes absolute number in patients after liver transplantation as well as reliable difference between cell number in patients with normal postoperative period and in patients with immune-mediated graft dysfunction allow considering T-lymphocyte subpopulation as a rejection predictor in the late post-transplant period. The correlation between CD8+ T-lymphocyte absolute number and the results of histological examination makes the former an alternative and, what is more, safe noninvasive method in early diagnostics of liver graft rejection.
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