A biomarker panel for acute graft-versus-host disease
A biomarker panel for acute graft-versus-host disease
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DOI：
10.1182/blood-2008-07-167098
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发表时间：
2009-01-08
期刊：
影响因子：
20.3
通讯作者：
Ferrara, James L. M.
中科院分区：
文献类型：
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作者：
Paczesny, Sophie;Krijanovski, Oleg I.;Ferrara, James L. M.
急性移植物抗宿主病（GVHD）尚无有效的生物标志物。我们用抗体微阵列筛选了42名接受移植的患者的血浆中的120种蛋白质，发现了8种诊断GVHD的潜在生物标志物。然后，我们通过酶联免疫吸附试验（ELISA）测量了424例接受移植的患者样本中这些生物标志物的水平，这些患者随机分为训练组（n = 282）和验证组（n = 142）。这8种蛋白质的逻辑回归分析确定了4种蛋白质（白细胞介素-2-受体-α、肿瘤坏死因子-受体-1、白细胞介素-8和肝细胞生长因子）的复合生物标志物组，其最佳地区分了患有和不患有GVHD的患者。在训练集中区分这2组的受试者工作特征曲线下面积为0.91（95%置信区间，0.87-0.94），在验证集中为0.86（95%置信区间，0.79-0.92）。在GVHD患者中，考克斯回归分析显示，生物标志物组预测生存率与GVHD严重程度无关。一组4种生物标志物可以在GVHD临床症状发作时确认患者中GVHD的诊断，并提供与GVHD严重程度无关的预后信息。（血。2009;113：273-278）
No validated biomarkers exist for acute graft-versus-host disease (GVHD). We screened plasma with antibody microarrays for 120 proteins in a discovery set of 42 patients who underwent transplantation that revealed 8 potential biomarkers for diagnostic of GVHD. We then measured by enzyme-linked immunosorbent assay (ELISA) the levels of these biomarkers in samples from 424 patients who underwent transplantation randomly divided into training (n = 282) and validation (n = 142) sets. Logistic regression analysis of these 8 proteins determined a composite biomarker panel of 4 proteins (interleukin-2-receptor-alpha, tumor-necrosis-factor-receptor-1, interleukin-8, and hepatocyte growth factor) that optimally discriminated patients with and without GVHD. The area under the receiver operating characteristic curve distinguishing these 2 groups in the training set was 0.91 (95% confidence interval, 0.87-0.94) and 0.86 (95% confidence interval, 0.79-0.92) in the validation set. In patients with GVHD, Cox regression analysis revealed that the biomarker panel predicted survival independently of GVHD severity. A panel of 4 biomarkers can confirm the diagnosis of GVHD in patients at onset of clinical symptoms of GVHD and provide prognostic information independent of GVHD severity. (Blood. 2009;113:273-278)