Functionally significant renal allograft rejection is defined by transcriptional criteria
Functionally significant renal allograft rejection is defined by transcriptional criteria
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DOI：
10.1111/j.1600-6143.2005.00719.x
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发表时间：
2005-03-01
影响因子：
8.8
通讯作者：
Kirk, AD
中科院分区：
文献类型：
--
作者：
Hoffmann, SC;Hale, DA;Kirk, AD
同种异体肾移植急性细胞排斥（ACR）是一种 T 细胞介导的疾病，可通过组织学诊断。然而，许多功能正常的同种异体移植物有 T 细胞浸润和组织学 ACR，许多非免疫过程导致同种异体移植物功能障碍。因此，组织学和功能标准都不足以确定明显的排斥反应，并且临床排斥反应的基本特征仍未定义。为了区分同种异体移植淋巴细胞浸润和临床显着的 ACR，我们将 ACR 患者的肾活检与以下患者的肾活检进行了比较： 亚临床排斥（SCR，功能稳定且组织学排斥）；没有拒绝；和非移植肾脏。通过 RT-PCR 对活检组织进行组织学和转录比较，以了解 72 个相关免疫功能基因。渗透物的程度和成分均未定义 ACR。然而，转录因子在效应 T(H)1T 细胞激活过程中上调，最显着的是转录因子 T-bet、效应受体 Fas 配体和共刺激分子 CD152 清楚地区分了患者类别（p = 0.001）。其他基因的转录本在 SCR 和 ACR 中也同样升高，表明它们与浸润相关，而不是功能障碍。具有临床意义的 ACR 不仅仅由浸润的大小或组成来定义，而是由浸润细胞的转录活性来定义。对选定基因转录本的定量分析可以增强同种异体移植物的临床评估。
Renal allograft acute cellular rejection (ACR) is a T-cell mediated disease that is diagnosed histologically. However, many normally functioning allografts have T-cell infiltrates and histological ACR, and many nonimmune processes cause allograft dysfunction. Thus, neither histological nor functional criteria are sufficient to establish a significant rejection, and the fundamental features of clinical rejection remain undefined. To differentiate allograft lymphocyte infiltration from clinically significant ACR, we compared renal biopsies from patients with ACR to patients with: sub-clinical rejection (SCR, stable function with histological rejection); no rejection; and nontransplanted kidneys. Biopsies were compared histologically and transcriptionally by RT-PCR for 72 relevant immune function genes. Neither the degree nor the composition of the infiltrate defined ACR. However, transcripts up-regulated during effector T(H)1T-cell activation, most significantly the transcription factor T-bet, the effector receptor Fas ligand and the costimulation molecule CD152 clearly (p = 0.001) distinguished the patient categories. Transcripts from other genes were equivalently elevated in SCR and ACR, indicating their association with infiltration, not dysfunction. Clinically significant ACR is not defined solely by the magnitude nor composition of the infiltrate, but rather by the transcriptional activity of the infiltrating cells. Quantitative analysis of selected gene transcripts may enhance the clinical assessment of allografts.