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托珠单抗对肾移植慢性抗体介导排斥反应(cAMR)的显著疗效

The Promising Effect of Tocilizumab on Chronic Antibody-Mediated Rejection (cAMR) of Kidney Transplant.

作者信息

Świątek Łukasz, Miedziaszczyk Miłosz, Lewandowski Dominik, Robakowski Filip, Tyburski Piotr, Jakubowska Marta, Karczewski Marek, Idasiak-Piechocka Ilona

机构信息

Students Research Group of Transplantation and Kidney Diseases, Poznan University of Medical Sciences, 60-355 Poznan, Poland.

Department of General and Transplant Surgery, Poznan University of Medical Sciences, 60-355 Poznan, Poland.

出版信息

Pharmaceutics. 2025 Jan 9;17(1):78. doi: 10.3390/pharmaceutics17010078.

DOI:10.3390/pharmaceutics17010078
PMID:39861726
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11768637/
Abstract

: Chronic antibody-mediated rejection (cAMR) constitutes a serious challenge in the long-term success of organ transplantation. It is associated with donor-specific antibodies (DSAs) which activate a complement pathway in response to the presence of human leukocyte antigens (HLAs) on the graft, which results in chronic inflammation and leads to graft dysfunction. One of the recent promising methods of cAMR treatment is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody referred to as Tocilizumab (TCZ). The aim of the presented systematic review is to explore the existing knowledge regarding the effect of tocilizumab treatment on cAMR and to perform a meta-analysis of the available data. : A systematic review was performed using the PRISMA 2020 Checklist and Flow diagram. A systematic review protocol was registered in PROSPERO: CRD42024510996. The bias assessment was obtained with Methodical Index for Non-Randomized Studies (MINORS), whereas meta-analysis was performed using MedCalc. : Five clinical trials with a total number of 105 patients were included in our review. The mean loss of eGFR in time was -0.141 mL/min/1.73 m (95% CI: -0.409 to 0.126; = 0.298) and was found to be statistically insignificant. The heterogeneity was low and was equal to I = 0.00%. The authors demonstrated a reduction in DSA titer by TCZ (-0.266 MFI (95% CI: -0.861 to 0.329; = 0.377)). In the majority of studies, eGFR stabilization was associated with a reduction in DSAs. : TCZ pharmacotherapy insignificantly reduced DSA titer and eGFR. Despite promising outcomes of potential eGFR stabilization, there is a need for large randomized controlled trials comparing standard management of cAMR and tocilizumab treatment.

摘要

慢性抗体介导的排斥反应(cAMR)是器官移植长期成功面临的一项严峻挑战。它与供体特异性抗体(DSA)相关,这些抗体在移植物上存在人类白细胞抗原(HLA)时会激活补体途径,进而导致慢性炎症并引发移植物功能障碍。cAMR治疗的一种近期有前景的方法是一种重组人源化抗白细胞介素-6受体(IL-6R)单克隆抗体,称为托珠单抗(TCZ)。本系统评价的目的是探索关于托珠单抗治疗对cAMR影响的现有知识,并对现有数据进行荟萃分析。

使用PRISMA 2020清单和流程图进行了系统评价。系统评价方案已在PROSPERO注册:CRD42024510996。使用非随机研究的方法学指数(MINORS)进行偏倚评估,而荟萃分析则使用MedCalc进行。

我们的评价纳入了五项临床试验,共有105名患者。随时间推移的估计肾小球滤过率(eGFR)平均下降为-0.141 mL/min/1.73 m²(95%置信区间:-0.409至0.126;P = 0.298),且发现无统计学意义。异质性较低,等于I² = 0.00%。作者证明托珠单抗可降低DSA滴度(-0.266平均荧光强度(MFI)(95%置信区间:-0.861至0.329;P = 0.377))。在大多数研究中,eGFR稳定与DSA减少相关。

托珠单抗药物治疗对DSA滴度和eGFR的降低无显著意义。尽管潜在的eGFR稳定有良好结果,但仍需要大型随机对照试验来比较cAMR的标准管理与托珠单抗治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4e7/11768637/3d46630e84d7/pharmaceutics-17-00078-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4e7/11768637/a7cae67c0f20/pharmaceutics-17-00078-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4e7/11768637/f9449abcfabe/pharmaceutics-17-00078-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4e7/11768637/3d46630e84d7/pharmaceutics-17-00078-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4e7/11768637/a7cae67c0f20/pharmaceutics-17-00078-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4e7/11768637/745e012e74df/pharmaceutics-17-00078-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4e7/11768637/5e6ad24b265e/pharmaceutics-17-00078-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4e7/11768637/a311db57655f/pharmaceutics-17-00078-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4e7/11768637/f9449abcfabe/pharmaceutics-17-00078-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4e7/11768637/3d46630e84d7/pharmaceutics-17-00078-g006.jpg

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The Banff 2022 Kidney Meeting Report: Reappraisal of microvascular inflammation and the role of biopsy-based transcript diagnostics.班夫 2022 年肾脏会议报告:重新评估微血管炎症和基于活检的转录诊断学的作用。
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Tocilizumab in the treatment of active chronic humoral rejection resistant to standard therapy.托珠单抗治疗对标准治疗抵抗的活动性慢性体液排斥反应。
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