Bile duct regeneration and immune response by passenger lymphocytes signals biliary recovery versus complications after liver transplantation
Bile duct regeneration and immune response by passenger lymphocytes signals biliary recovery versus complications after liver transplantation
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胆管再生和过客淋巴细胞的免疫反应表明胆汁恢复与肝移植后并发症的关系
DOI：
10.1002/lt.24836
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发表时间：
2017
影响因子：
4.6
通讯作者：
Brunner SM
中科院分区：
文献类型：
--
作者：
Junger HH;Schlitt HJ;Geissler EK;Fichtner-Feigl S;Brunner SM
本研究旨在阐明上皮再生反应和免疫细胞浸润对肝移植术后胆道并发症的影响。在41例患者中，通过BD损伤评分量化冷藏后的胆管（BD）损伤，并与患者结局相关。用荧光原位杂交（FISH）检测细菌浸润情况。通过免疫组织化学分析BD样本的E-钙粘蛋白、细胞角蛋白、CD 56、CD 14、CD 4、CD 8，以及通过双重免疫荧光分析细胞因子的产生，并通过信使RNA（mRNA）微阵列分析。与胆道并发症患者受损的BD相比，无胆道并发症患者受损的BD中粘附连接的mRNA水平升高（P< 0.01）。免疫组化显示无胆道并发症的BD中E‐钙粘蛋白和细胞角蛋白表达增加（P= 0.03;P= 0.047）。荧光原位杂交分析显示细菌在BD中移位。而mRNA分析提示无胆道并发症的BD患者免疫应答增强（P< 0.01）。在免疫细胞浸润方面，无并发症患者的CD 4+和CD 8+细胞显著高于有并发症患者（P= 0.02;P= 0.01）。总之，在冷藏期间BD损伤后，我们假设胆管上皮的功能再生能力和增强的局部适应性免疫细胞浸润对BD恢复至关重要。因此，这种分子免疫学BD分析可以帮助预测冷藏后“主要”上皮损伤病例的胆道并发症。肝脏移植23 1422-1432 2017 AASLD。
This study aimed to elucidate the impact of epithelial regenerative responses and immune cell infiltration on biliary complications after liver transplantation. Bile duct (BD) damage after cold storage was quantified by a BD damage score and correlated with patient outcome in 41 patients. Bacterial infiltration was determined by fluorescence in situ hybridization (FISH). BD samples were analyzed by immunohistochemistry for E‐cadherin, cytokeratin, CD56, CD14, CD4, CD8, and double‐immunofluorescence for cytokine production and by messenger RNA (mRNA) microarray. Increased mRNA levels of adherens junctions (P< 0.01) were detected in damaged BDs from patients without complications compared with damaged BDs from patients with biliary complications. Immunohistochemistry showed increased expression of E‐cadherin and cytokeratin in BDs without biliary complications (P= 0.03;P= 0.047). FISH analysis demonstrated translocation of bacteria in BDs. However, mRNA analysis suggested an enhanced immune response in BDs without biliary complications (P< 0.01). Regarding immune cell infiltration, CD4+and CD8+cells were significantly increased in patients without complications compared with those with complications (P= 0.02;P= 0.01). In conclusion, following BD damage during cold storage, we hypothesize that the functional regenerative capacity of biliary epithelium and enhanced local adaptive immune cell infiltration are crucial for BD recovery. Such molecular immunological BD analyses therefore could help to predict biliary complications in cases of “major” epithelial damage after cold storage.Liver Transplantation 23 1422–1432 2017AASLD.