Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes.
Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes.
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DOI：
10.1038/ki.2011.245
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发表时间：
2011-12
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
作者：
进行性慢性组织学损害的程度与移植肾长期存活率相关。为了确定有前途的分子靶点，及时干预，我们检查了肾移植方案和适应症活检从120个低风险的儿童和青少年受者的全基因组微阵列表达谱。在数据驱动的分析中，我们发现了适应性和先天免疫基因表达的高度调节模式，其与已建立或正在进行的组织学慢性损伤相关，并且还与未来慢性组织学损伤的发展相关，即使在组织学原始肾脏中也是如此。因此，在分子水平上组织学上未识别的免疫损伤为慢性组织损伤的发展奠定了基础，而在建立和恶化的慢性同种异体移植物损伤期间，相同的分子反应会加重。无论假设的慢性同种异体移植物损伤的免疫或非免疫触发，先天性和适应性免疫反应的高度协调的调节被发现在移植物在分子水平上。这发生在组织学病变出现前几个月，定量低于经典T细胞或抗体介导的排斥反应的诊断阈值。因此，测量特定的免疫基因表达的协议活检可能是必要的，以预测随后的慢性损伤的发展，在组织学上静止的移植物，并作为一种手段，滴定免疫抑制治疗。
The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
6.2
作者：
Nankivell, BJ;Fenton-Lee, CA;Chapman, JR
通讯作者：
Chapman, JR
影响因子：
8.8
作者：
Cosio, FG;Grande, JP;Stegall, MD
通讯作者：
Stegall, MD
影响因子：
13.6
作者：
Naesens, Maarten;Lerut, Evelyne;Kuypers, Dirk R. J.
通讯作者：
Kuypers, Dirk R. J.
影响因子：
13.6
作者：
Ojo, AO;Hanson, JA;Port, FK
通讯作者：
Port, FK