Low Paneth cell numbers at onset of gastrointestinal graft-versus-host disease identify patients at high risk for nonrelapse mortality
Low Paneth cell numbers at onset of gastrointestinal graft-versus-host disease identify patients at high risk for nonrelapse mortality
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DOI：
10.1182/blood-2013-02-485813
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发表时间：
2013-08-22
期刊：
影响因子：
20.3
通讯作者：
Holler, Ernst
中科院分区：
文献类型：
--
作者：
Levine, John E.;Huber, Elisabeth;Holler, Ernst
胃肠道急性移植物抗宿主病（GVHD）是异基因造血细胞移植后常见的致死性并发症。临床严重程度与结果相关，但组织病理学分级主要用于确认临床诊断。使用组织病理学分级来预测临床结果的一个障碍是移植中心之间的分级者差异。最近的实验模型表明，位于小肠中并通过分泌抗菌肽帮助调节GI微生物组的潘氏细胞的损失与临床GVHD严重程度相关。由于潘氏细胞很容易通过光学显微镜进行识别和定量，我们评估了在2个不同中心诊断GI GVHD时获得的116份十二指肠活检组织中每高倍视野（hpf）潘氏细胞的平均数量及其临床结局。潘氏细胞计数在各中心之间具有重复性（r（2）= 0.81; P <0.0001）。诊断时潘氏细胞数量较低与临床上更严重的GI GVHD（P < .0001）和对GVHD治疗反应的可能性较低（P < .0001）相关。根据非复发死亡率，每hpf 4个潘氏细胞的阈值对患者进行分层（28% vs 56%; P = 0.004）。我们的结论是，十二指肠潘氏细胞计数是一个容易获得的疾病严重程度的指标，提供了重要的信息GVHD预后。
Acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract is an often lethal complication of allogeneic hematopoietic cell transplant. Clinical severity correlates with outcomes, but histopathologic grading is primarily used to confirm the clinical diagnosis. One barrier to using histopathologic grading to predict clinical outcomes is inter-grader variability among transplant centers. Recent experimental models have shown that the loss of Paneth cells, which are located in the small intestine and help regulate the GI microbiome by secreting antimicrobial peptides, correlates with clinical GVHD severity. Because Paneth cells are easy to identify and quantify by light microscopy, we evaluated the mean number of Paneth cells per high-powered field (hpf) in 116 duodenal biopsies obtained at diagnosis of GI GVHD at 2 different centers with their clinical outcomes. Paneth cell counts were reproducible between centers (r(2) = 0.81; P < .0001). Lower numbers of Paneth cells at diagnosis correlated with clinically more severe GI GVHD (P < .0001) and less likelihood of response to GVHD treatment (P < .0001). A threshold of 4 Paneth cells per hpf stratified patients according to nonrelapse mortality (28% vs 56%; P = .004). We conclude that the enumeration of duodenal Paneth cells is a readily available index of disease severity that provides important information regarding GVHD prognosis.