Discrete serum protein signatures discriminate between human retrovirus-associated hematologic and neurologic disease
Discrete serum protein signatures discriminate between human retrovirus-associated hematologic and neurologic disease
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DOI：
10.1038/sj.leu.2403781
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发表时间：
2005-07-01
期刊：
影响因子：
11.4
通讯作者：
Jacobson, S
中科院分区：
文献类型：
--
作者：
Semmes, OJ;Cazares, LH;Jacobson, S
人类T细胞白血病病毒I型（HTLV-I）是成人T细胞白血病（ATL）和HTLV-I相关脊髓病/热带痉挛性下肢轻瘫（HAM/TSP）的病原体。大约5%的受感染者会发展成任何一种疾病，目前还没有早期检测或准确评估疾病状态的诊断工具。我们已经使用质谱法对血清蛋白质进行高通量表达谱分析，以鉴定可以区分HTLV-1感染个体的疾病状态的蛋白质表达模式。研究组包括42例ATL、50例HAM/TSP和38例正常对照。对应于肽离子的光谱峰由MS-TOF数据产生。我们应用分类和回归树分析建立了一个决策算法，在三个组中达到了77%的正确分类率。使用10个ATL、10个HAM和10个对照样品的第二组来验证该结果。进行线性判别分析以验证和可视化类别分离。亲和层析和分子筛层析结合串联质谱用于鉴定ATL中特异性过表达的三个峰：α胰蛋白酶抑制剂的11.7 kDa片段和血红蛋白-2的2个连续片段（19.9和11.9 kDa）。据我们所知，这是第一次应用蛋白质谱来区分由单一感染因子引起的两种疾病状态。
The human T-cell leukemia virus type I (HTLV-I) is the causative agent for adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Approximately 5% of infected individuals will develop either disease and currently there are no diagnostic tools for early detection or accurate assessment of disease state. We have employed high- throughput expression profiling of serum proteins using mass spectrometry to identify protein expression patterns that can discern between disease states of HTLV-I- infected individuals. Our study group consisted of 42 ATL, 50 HAM/TSP, and 38 normal controls. Spectral peaks corresponding to peptide ions were generated from MS-TOF data. We applied Classification and Regression Tree analysis to build a decision algorithm, which achieved 77% correct classification rate across the three groups. A second cohort of 10 ATL, 10 HAM and 10 control samples was used to validate this result. Linear discriminate analysis was performed to verify and visualize class separation. Affinity and sizing chromatography coupled with tandem mass spectrometry was used to identify three peaks specifically overexpressed in ATL: an 11.7 kDa fragment of alpha trypsin inhibitor, and two contiguous fragments (19.9 and 11.9 kDa) of haproglobin-2. To the best of our knowledge, this is the first application of protein profiling to distinguish between two disease states resulting from a single infectious agent.