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一名肾移植患者出现涉及细胞凋亡的肾小管周围毛细血管损伤的异常模式。

An unusual pattern of peritubular capillary injury involving apoptosis in a renal transplant patient.

作者信息

Brealey John K, Cassidy John, Manavis Jim

机构信息

a Department of Anatomical Pathology , SA Pathology , Adelaide , Australia.

b Department of Immunology , SA Pathology , Adelaide , Australia.

出版信息

Ultrastruct Pathol. 2018 Jul-Aug;42(4):323-332. doi: 10.1080/01913123.2018.1484542. Epub 2018 Jun 13.

DOI:10.1080/01913123.2018.1484542
PMID:29897310
Abstract

Microvascular injury is an important factor in renal allograft survival. Repeated episodes of endothelial injury from chronic antibody-mediated rejection typically manifest at the ultrastructural level as circumferential multilayering of remodeled glomerular basement membrane material and peritubular capillary basal lamina. In contrast to this typical pattern of microvascular injury, a renal transplantation case is presented in which focally dilated and multilayered segments of peritubular capillary basal lamina bearing lipid droplets were interspersed with ultrastructurally normal unilayered segments of basal lamina devoid of lipid droplets. Glomerular basement membranes were not affected by this process. The peak incidence of lipid droplets within the peritubular capillary walls coincided with a peak in apoptotic activity within the allograft. Lesser amounts of the same lipidic material were identified in the mesangial matrix and an arteriolar wall. Mesangial electron-dense deposits were detected at two weeks posttransplantation and their appearance coincided with elevated immunological activity in the glomeruli, as determined by immunofluorescence microscopy. The unusual ultrastructure and immunological activity observed in this case may reflect a process of impaired apoptotic clearance within the allograft. The six biopsies from a single patient are discussed in the setting of a highly sensitized renal transplant recipient who received prophylactic terminal complement blockade by eculizumab. The findings may be relevant to the study of apoptosis, efferocytosis, microvascular injury, eculizumab, rejection, lupus, and drug-related disease.

摘要

微血管损伤是肾移植存活的一个重要因素。慢性抗体介导的排斥反应导致的反复内皮损伤,在超微结构水平上通常表现为重塑的肾小球基底膜物质和肾小管周围毛细血管基底膜的周向多层化。与这种典型的微血管损伤模式不同,本文报道了一例肾移植病例,其中肾小管周围毛细血管基底膜的局灶性扩张和多层化区域含有脂滴,与超微结构正常的无脂滴单层基底膜区域相间分布。肾小球基底膜未受此过程影响。肾小管周围毛细血管壁内脂滴的发生率峰值与移植肾内凋亡活性的峰值一致。在系膜基质和小动脉壁中也发现了少量相同的脂质物质。移植后两周检测到系膜电子致密沉积物,其出现与肾小球免疫活性升高一致,这是通过免疫荧光显微镜确定的。该病例中观察到的异常超微结构和免疫活性可能反映了移植肾内凋亡清除受损的过程。本文在一名高度致敏的肾移植受者接受依库珠单抗预防性终末补体阻断的背景下,讨论了该患者的六次活检结果。这些发现可能与凋亡、胞葬作用、微血管损伤、依库珠单抗、排斥反应、狼疮及药物相关疾病的研究有关。

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