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肾移植中的免疫抑制教训:撤退还是坚守?

A Lesson of Immunosuppression in Renal Transplant: Retreat or Hold?

机构信息

Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education NHC Key Laboratory of Organ Transplantation Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.

Department of Thyroid Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Yale J Biol Med. 2023 Mar 31;96(1):57-77. doi: 10.59249/XGIO3365. eCollection 2023 Mar.

Abstract

: Aiming at understanding whether there are cases of near-tolerance among long-term surviving kidney transplant recipients in our center, or even operant tolerance can be attempted based on their immune status, we analyzed changes of immune cell subsets and cytokines in various groups, and evaluated immune status of long-term survival recipients. : A real-world, observational, retrospective cohort study was conducted in our hospital. Twenty-eight long-term recipients were selected as study subjects, 15 recent postoperative stable recipients, and 15 healthy subjects as controls. T and B lymphocyte subsets, MDSCs, and cytokines were detected and analyzed. : Treg/CD4 T cells, total B and B10 cells in long-term and recent renal recipients were lower than healthy controls (HC). The level of IFN-γ and IL-17A in long-term survival patients was obviously higher than that in recent postoperative stable recipients and HC, while TGF-β1 level was significantly lower in long-term survival group than in short-term postoperative group and HC. Notably, compared with short-term recipients, it has been found that the IL-6 level in both positive and negative HLA groups were obviously lower (all <0.05). In the long-term survival group, 43% of recipients were positive for urinary protein and 50% were positive for HLA antibody. : This "real-world" study validates the findings of real status of long-term survival recipients observed in clinical trials. Contrary to a state of proper tolerance as expected, the group recipients in long-term survival were accompanied by the increased indicators of immune response, while those related to immune tolerance were not significantly increased. Long-term survival recipients with stable renal function may be in an immune equilibrium state where immunosuppression and rejection coexist under the action of low-intensity immune agents. If immunosuppressive agents are reduced or even removed, rejection may occur.

摘要

:为了了解我们中心的长期存活肾移植受者是否存在接近耐受的情况,甚至可以根据他们的免疫状态尝试获得操作性耐受,我们分析了各组免疫细胞亚群和细胞因子的变化,并评估了长期存活受者的免疫状态。:本研究为医院开展的真实世界、观察性、回顾性队列研究。选择 28 例长期存活受者作为研究对象,其中 15 例为近期术后稳定受者,15 例为健康对照者。检测和分析 T、B 淋巴细胞亚群、MDSC 和细胞因子。:长期和近期肾移植受者的 Treg/CD4 T 细胞、总 B 和 B10 细胞均低于健康对照组(HC)。长期存活患者的 IFN-γ和 IL-17A 水平明显高于近期术后稳定受者和 HC,而 TGF-β1 水平在长期存活组明显低于短期术后组和 HC。值得注意的是,与短期受者相比,发现 HLA 阳性和阴性组的 IL-6 水平均明显降低(均<0.05)。在长期存活组中,43%的受者尿蛋白阳性,50%的受者 HLA 抗体阳性。:这项“真实世界”研究验证了临床试验中观察到的长期存活受者真实状态的研究结果。与预期的适当耐受状态相反,长期存活组受者伴有免疫反应指标的增加,而与免疫耐受相关的指标没有明显增加。肾功能稳定的长期存活受者可能处于免疫平衡状态,在低强度免疫制剂的作用下,免疫抑制和排斥同时存在。如果减少甚至去除免疫抑制剂,可能会发生排斥反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fec/10052597/8daa4c7829de/yjbm_96_1_57_g01.jpg

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