The Nature of Biopsies with "Borderline Rejection" and Prospects for Eliminating This Category
The Nature of Biopsies with "Borderline Rejection" and Prospects for Eliminating This Category
复制标题
DOI：
10.1111/j.1600-6143.2011.03784.x
复制
发表时间：
2012-01-01
影响因子：
8.8
通讯作者：
Halloran, P. F.
中科院分区：
文献类型：
--
作者：
de Freitas, D. G.;Sellares, J.;Halloran, P. F.
在肾移植中，许多炎症活检的变化不足以称为T细胞介导的排斥反应（TCMR）被标记为边界，使管理不确定。这项研究探讨了边界活检的性质，作为最终消除这一类别的一个步骤。我们比较了40例临界、35例TCMR和116例非排斥活检。TCMR活检的炎症多于交界性，但程度相似的小管炎和瘢痕。令人惊讶的是，活检后的功能恢复在所有类别中是相似的，表明对治疗的反应对于定义TCMR是不可靠的。我们使用微阵列研究了TCMR、临界和非排斥的分子变化，测量了四个已发表的特征：T细胞负荷;排斥分类器;典型TCMR分类器;和风险评分。这些边缘活检重新分配为TCMR样13/40（33%）或非排斥样27/40（67%）。组织学诊断分子定义的TCMR为边界的一个主要原因是萎缩-瘢痕形成，这干扰了炎症和小管炎的评估。决策树分析显示，在85%的病例中，i-total>27%和小管炎程度>3%与TCMR的分子诊断相匹配。总之，大多数病例的组织病理学指定的边界被发现是非排斥反应的分子表型。分子测量和组织病理学都为临床验证后更精确地分配这些病例提供了机会。
In kidney transplantation, many inflamed biopsies with changes insufficient to be called T-cell-mediated rejection (TCMR) are labeled borderline, leaving management uncertain. This study examined the nature of borderline biopsies as a step toward eventual elimination of this category. We compared 40 borderline, 35 TCMR and 116 nonrejection biopsies. TCMR biopsies had more inflammation than borderline but similar degrees of tubulitis and scarring. Surprisingly, recovery of function after biopsy was similar in all categories, indicating that response to treatment is unreliable for defining TCMR. We studied the molecular changes in TCMR, borderline and nonrejection using microarrays, measuring four published features: T-cell burden; a rejection classifier; a canonical TCMR classifier; and risk score. These reassigned borderline biopsies as TCMR-like 13/40 (33%) or nonrejection-like 27/40 (67%). A major reason that histology diagnosed molecularly defined TCMR as borderline was atrophy-scarring, which interfered with assessment of inflammation and tubulitis. Decision tree analysis showed that i-total >27% and tubulitis extent >3% match the molecular diagnosis of TCMR in 85% of cases. In summary, most cases designated borderline by histopathology are found to be nonrejection by molecular phenotyping. Both molecular measurements and histopathology offer opportunities for more precise assignment of these cases after clinical validation.