Defining the Canonical Form of T-Cell-Mediated Rejection in Human Kidney Transplants
Defining the Canonical Form of T-Cell-Mediated Rejection in Human Kidney Transplants
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DOI：
10.1111/j.1600-6143.2009.03007.x
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发表时间：
2010-04-01
影响因子：
8.8
通讯作者：
Halloran, P. F.
中科院分区：
文献类型：
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作者：
Famulski, K. S.;Einecke, G.;Halloran, P. F.
班夫定义T细胞介导的排斥反应（TCMR）使用非特异性病变和任意截止，没有外部金标准。我们重新研究的特点，TCMR使用专门的分子定义独立的组织病理学。该定义来源于具有完全发育的TCMR的小鼠肾移植，并且基于反映IFNG效应和替代性巨噬细胞活化的转录物的高表达。在234例人类肾移植活检的原因表型微阵列，我们确定了26个活检符合这些标准。在排除3例不相关疾病的活检后，所有23例活检均具有典型的TCMR Banff病变（炎症，小管炎），其中10/23例有v病变。Banff组织病理学诊断18例为TCMR，1例为混合型，4例为临界型。尽管转录组的显著变化表明组织损伤和去分化，但所有具有分子定义的TCMR的肾脏，即使具有v病变或晚期排斥，在6个月时也表现出良好的功能恢复，没有移植物丢失（平均随访2.5年）。因此，完全由分子定义的TCMR表现出与TCMR相关的病变和功能损害，但恢复和生存良好，即使有晚期排斥反应或动脉炎。这种病理、临床和分子特征的组合构成了典型的或典型的T细胞介导的排斥。
Banff defines T-cell-mediated rejection (TCMR) using nonspecific lesions and arbitrary cutoffs, with no external gold standard. We reexamined features of TCMR using exclusively molecular definition independent of histopathology. The definition was derived from mouse kidney transplants with fully developed TCMR, and is based on high expression of transcripts reflecting IFNG effects and alternative macrophage activation. In 234 human kidney transplant biopsies for cause phenotyped by microarrays, we identified 26 biopsies meeting these criteria. After excluding three biopsies with unrelated diseases, all 23 biopsies had typical Banff lesions of TCMR (inflammation, tubulitis), with v lesions in 10/23. Banff histopathology diagnosed 18 as TCMR, 1 as mixed and 4 as borderline. Despite marked changes in transcriptome indicating tissue injury and dedifferentiation, all kidneys with molecularly defined TCMR, even with v lesions or late rejection, demonstrated excellent recovery of function at 6 months with no graft loss (mean follow-up 2.5 years). Thus TCMR defined exclusively by molecules manifests TCMR-related lesions and function impairment, but good recovery and survival, even with late rejection or arteritis. This combination of pathologic, clinical and molecular features constitutes the typical or canonical T-cell-mediated rejection.