Srinivasan Ramaprasad, Daniels Jasmine, Fusaro Vincent, Lundqvist Andreas, Killian Jonathan K, Geho David, Quezado Martha, Kleiner David, Rucker Sally, Espina Virginia, Whiteley Gordon, Liotta Lance, Petricoin Emmanuel, Pittaluga Stefania, Hitt Ben, Barrett A J, Rosenblatt Kevin, Childs Richard W
Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
Exp Hematol. 2006 Jun;34(6):796-801. doi: 10.1016/j.exphem.2006.02.013.
The rapid diagnosis of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT) is important for optimizing the management of this life-threatening complication. Current diagnostic techniques are time-consuming and require invasive tissue sampling. We investigated serum protein pattern analysis using surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectrometry as a tool to diagnose GVHD.
Eighty-eight serum samples were obtained from 34 patients undergoing HCT either pretransplant (n = 28 samples) or at various time points posttransplant (n = 60 samples), including 22 samples obtained on the day of onset of acute GVHD symptoms. Serum proteomic spectra generated from a "training set" of known samples were used to identify distinct proteomic patterns that best categorized a sample as either pretransplant, posttransplant non-GVHD, or GVHD; these distinct proteomic signatures were subsequently used to classify samples from a masked "test" sample set into the appropriate diagnostic category.
Proteomic pattern analysis accurately distinguished GVHD samples from both posttransplant non-GVHD samples and pretransplant samples (100% specificity and 100% sensitivity in both cases). Furthermore, distinct serum proteomic signatures were identified that distinguished pretransplant from posttransplant non-GVHD samples (100% specificity and 94% sensitivity).
These preliminary data suggest a potential application of SELDI-TOF-based proteomic analysis as a rapid and accurate method to diagnose acute GVHD.
异基因造血细胞移植（HCT）后急性移植物抗宿主病（GVHD）的快速诊断对于优化这种危及生命的并发症的管理非常重要。目前的诊断技术耗时且需要进行侵入性组织采样。我们研究了使用表面增强激光解吸电离飞行时间（SELDI-TOF）质谱分析血清蛋白模式作为诊断GVHD的工具。
从34例接受HCT的患者中获取了88份血清样本，其中移植前（n = 28份样本）或移植后不同时间点（n = 60份样本），包括在急性GVHD症状发作当天获取的22份样本。由已知样本的“训练集”生成的血清蛋白质组谱用于识别不同的蛋白质组模式，这些模式能将样本最佳地分类为移植前、移植后非GVHD或GVHD；随后，这些不同的蛋白质组特征被用于将来自隐蔽的“测试”样本集的样本分类到适当的诊断类别中。
蛋白质组模式分析能够准确地区分GVHD样本与移植后非GVHD样本以及移植前样本（两种情况下特异性和敏感性均为100%）。此外，还识别出了不同的血清蛋白质组特征，可区分移植前与移植后非GVHD样本（特异性为100%，敏感性为94%）。
这些初步数据表明基于SELDI-TOF的蛋白质组分析作为一种快速准确诊断急性GVHD的方法具有潜在应用价值。
