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肾移植活检中伴临界性T细胞介导排斥反应的肥大细胞及其与慢性化的关系

Mast Cells in Kidney Transplant Biopsies With Borderline T Cell-mediated Rejection and Their Relation to Chronicity.

作者信息

Varol Hilal, van der Elst Guus, Baan Carla C, van Baardwijk Myrthe, Hesselink Dennis A, Duong van Huyen Jean-Paul, Kramann Rafael, Rabant Marion, van den Bosch Thierry P P, Clahsen-van Groningen Marian C

机构信息

Department of Pathology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.

出版信息

Transplant Direct. 2023 Apr 20;9(5):e1480. doi: 10.1097/TXD.0000000000001480. eCollection 2023 May.

DOI:10.1097/TXD.0000000000001480
PMID:37096153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10121434/
Abstract

UNLABELLED

Mast cells are potential contributors to chronic changes in kidney transplants (KTx). Here, the role of mast cells (MCs) in KTx is investigated in patients with minimal inflammatory lesions.

METHODS

Fourty-seven KTx biopsies (2009-2018) with borderline pathological evidence for T cell-mediated rejection according to the Banff'17 Update were retrospectively included and corresponding clinical data was collected. Immunohistochemistry for tryptase was performed on formalin-fixed paraffin-embedded sections. Cortical MCs were counted and corrected for area (MC/mm²). Interstitial fibrosis was assessed by Sirius Red staining and quantified using digital image analysis (QuPath).

RESULTS

Increased MC number was correlated to donor age (spearman's r = 0.35, = 0.022), deceased donor kidneys (mean difference = 0.74, t [32.5] = 2.21, = 0.035), and delayed graft function (MD = 0.78, t [33.9] = 2.43, = 0.020). Increased MC number was also correlated to the amount of interstitial fibrosis (r = 0.42, = 0.003) but did not correlate with transplant function over time (r = -0.14 = 0.36). Additionally, transplant survival 2 y post-biopsy was not correlated to MC number (mean difference = -0.02, t [15.36] = -0.06, = 0.96).

CONCLUSIONS

MC number in suspicious (borderline) for acute T cell-mediated rejection is correlated to interstitial fibrosis and time post-transplantation, suggesting MCs to be a marker for cumulative burden of tissue injury. There was no association between MCs and transplant function over time or transplant survival 2 y post-biopsy. It remains unclear whether MCs are just a bystander or have pro-inflammatory or anti-inflammatory effects in the KTx with minimal lesions.

摘要

未标记

肥大细胞是肾移植(KTx)慢性变化的潜在促成因素。在此,研究了肥大细胞(MCs)在炎症病变轻微的肾移植患者中的作用。

方法

回顾性纳入了47例根据Banff'17更新标准有T细胞介导排斥反应的临界病理证据的肾移植活检样本(2009 - 2018年),并收集了相应的临床数据。在福尔马林固定石蜡包埋切片上进行嗜酸性粒细胞阳离子蛋白免疫组织化学检测。对皮质肥大细胞进行计数并根据面积校正(肥大细胞/mm²)。通过天狼星红染色评估间质纤维化,并使用数字图像分析(QuPath)进行量化。

结果

肥大细胞数量增加与供体年龄相关(斯皮尔曼相关系数r = 0.35,P = 0.022)、脑死亡供体肾相关(平均差异 = 0.74,t[32.5] = 2.21,P = 0.035)以及移植肾功能延迟相关(MD = 0.78,t[33.9] = 2.43,P = 0.020)。肥大细胞数量增加也与间质纤维化程度相关(r = 0.42,P = 0.003),但与移植后随时间的功能无关(r = -0.14,P = 0.36)。此外,活检后2年的移植存活率与肥大细胞数量无关(平均差异 = -0.02,t[15.36] = -0.06,P = 0.96)。

结论

急性T细胞介导排斥反应可疑(临界)的肾移植中肥大细胞数量与间质纤维化及移植后时间相关,提示肥大细胞是组织损伤累积负担的标志物。肥大细胞与移植后随时间的功能或活检后2年的移植存活率之间无关联。目前尚不清楚在病变轻微的肾移植中,肥大细胞仅仅是旁观者还是具有促炎或抗炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f967/10121434/9231f25ee655/txd-9-e1480-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f967/10121434/4f4d74c5bbad/txd-9-e1480-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f967/10121434/7d2eae3d3c1d/txd-9-e1480-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f967/10121434/d08ffeb208e0/txd-9-e1480-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f967/10121434/f8fccb41861c/txd-9-e1480-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f967/10121434/9231f25ee655/txd-9-e1480-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f967/10121434/4f4d74c5bbad/txd-9-e1480-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f967/10121434/7d2eae3d3c1d/txd-9-e1480-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f967/10121434/d08ffeb208e0/txd-9-e1480-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f967/10121434/f8fccb41861c/txd-9-e1480-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f967/10121434/9231f25ee655/txd-9-e1480-g005.jpg

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IgE-Mediated Immune Response and Antibody-Mediated Rejection.免疫球蛋白 E 介导的免疫反应和抗体介导的排斥反应。
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Mast cell-mediated mechanistic pathways in organ transplantation.肥大细胞介导的器官移植中的机制途径。
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A 2018 Reference Guide to the Banff Classification of Renal Allograft Pathology.2018 年肾移植病理的班夫分类参考指南。
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