Expression of MHC Class I–Related Chain B (MICB) Molecules on Renal Transplant Biopsies-猫眼课题宝

MHC I 类相关链 B (MICB) 分子在肾移植活检中的表达

DOI：

发表时间：

2006

期刊：

Transplantation

影响因子：

6.2

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

I. Quiroga;M. Salio;D. Koo;L. Cerundolo;D. Shepherd;V. Cerundolo;S. Fuggle

背景。MICA和MICB （MHC I类相关链A和B）是编码MHC I类相关分子的多态性基因，在应激反应中在上皮细胞上表达。不相容的供体MIC抗原可刺激移植受者产生抗体。本研究旨在确定MICB在肾移植前和移植后的表达变化，并将其与炎症标志物和临床事件的变化联系起来。方法。活体供体（n=10）和尸体异体移植物（n=50）在移植前和移植后7天进行配对肾活检，进行MICB、白细胞浸润和HLA II类抗原染色。结果。在供体活检中，可变管状MICB表达明显[高6/60(10%)，低/阴性13/60(22%)，中间41/60(68%)]。移植后，17/60（28%）活检的肾小管MICB表达上调，并与MHC II类抗原诱导（P=0.02）和白细胞浸润（P=0.01）相关。急性肾小管坏死导致移植肾功能延迟（DGF）和急性排斥反应（AR）导致移植肾内的细胞应激。我们发现MICB表达上调与细胞应激之间存在很强的相关性，MICB表达上调的活检中有15/17有AR和/或DGF （P=0.003）。结论。这是第一个证明肾移植前MICB表达水平变化和肾移植后MICB表达诱导的研究。MICB的表达与HLAⅱ类抗原诱导、移植物的白细胞浸润和移植肾的细胞应激有关。MICB的表达对错配供体和受体的同种免疫反应有重要作用。

Background. MICA and MICB (MHC class I-related chain A and B) are polymorphic genes that encode molecules related to MHC class I and are expressed on epithelial cells in response to stress. Incompatible donor MIC antigens can stimulate antibody production in transplant recipients. This study was designed to determine MICB expression in kidney pretransplant and any subsequent changes in expression following transplantation and to correlate changes with inflammatory markers and clinical events. Methods. Paired renal biopsies obtained from living donor (n=10) and cadaveric allografts (n=50) before and 7 days posttransplant were stained for MICB, leukocytic infiltration, and HLA class II antigens. Results. Variable tubular MICB expression was evident in donor biopsies [high 6/60 (10%), low/negative 13/60 (22%), intermediate 41/60 (68%)]. Following transplantation, MICB was up-regulated on renal tubules of 17/60 (28%) biopsies and was associated with MHC class II antigen induction (P=0.02) and leukocyte infiltration (P=0.01). Acute tubular necrosis leading to delayed graft function (DGF) and acute rejection (AR) cause cellular stress within the transplanted kidney. We found a strong association between up-regulation of MICB and cellular stress, 15/17 biopsies with up-regulated MICB expression had AR and/or DGF (P=0.003). Conclusions. This is the first study demonstrating variable levels of MICB expression in kidneys before transplantation and induction of MICB expression following renal transplantation. MICB expression is associated with HLA class II antigen induction, leukocytic infiltration of the graft and cellular stress in the transplanted kidney. Expression of MICB could contribute significantly to the alloimmune response in mismatched donors and recipients.