Plasma proteome analysis in HTLV-1-associated myelopathy/tropical spastic paraparesis.
Plasma proteome analysis in HTLV-1-associated myelopathy/tropical spastic paraparesis.
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DOI：
10.1186/1742-4690-8-81
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发表时间：
2011-10-12
期刊：
影响因子：
3.3
通讯作者：
Bangham CR
中科院分区：
文献类型：
--
作者：
Kirk PD;Witkover A;Courtney A;Lewin AM;Wait R;Stumpf MP;Richardson S;Taylor GP;Bangham CR
人类嗜T淋巴细胞病毒1型（HTLV-1）引起中枢神经系统的慢性炎性疾病，称为HTLV-1相关性脊髓病/热带痉挛性下肢轻瘫（HAM），其类似于多发性硬化症（MS）的慢性脊髓形式。HAM的发病机制尚不清楚。为了帮助HAM的鉴别诊断和确定发病机制，我们分析了无症状HTLV-1携带者（AC）、HAM患者、未感染对照和MS患者的血浆蛋白质组。我们使用表面增强激光解吸电离（SELDI）质谱法分析了68名HTLV-1感染者的血浆蛋白质组（在两个非重叠组中，每组包括17名患有HAM和17名AC的患者）、16名未感染的对照和11名患有继发性进行性MS的患者。通过串联Q-TOF质谱鉴定候选生物标志物。三种血浆蛋白-高[β2-微球蛋白]、高[钙颗粒蛋白B]和低[载脂蛋白A2] -的浓度与HAM特异性相关，与前病毒负荷无关。血浆β2-微球蛋白水平与病情严重程度呈正相关。结果表明，单核细胞通过与HAM中活化的内皮细胞接触而被活化。单独使用β2-微球蛋白和钙粒蛋白B，我们推导出一种诊断算法，该算法正确分类了队列中81%的HTLV-1感染受试者的疾病状态（存在或不存在HAM）。
Human T lymphotropic virus Type 1 (HTLV-1) causes a chronic inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM) which resembles chronic spinal forms of multiple sclerosis (MS). The pathogenesis of HAM remains uncertain. To aid in the differential diagnosis of HAM and to identify pathogenetic mechanisms, we analysed the plasma proteome in asymptomatic HTLV-1 carriers (ACs), patients with HAM, uninfected controls, and patients with MS. We used surface-enhanced laser desorption-ionization (SELDI) mass spectrometry to analyse the plasma proteome in 68 HTLV-1-infected individuals (in two non-overlapping sets, each comprising 17 patients with HAM and 17 ACs), 16 uninfected controls, and 11 patients with secondary progressive MS. Candidate biomarkers were identified by tandem Q-TOF mass spectrometry. The concentrations of three plasma proteins - high [β2-microglobulin], high [Calgranulin B], and low [apolipoprotein A2] - were specifically associated with HAM, independently of proviral load. The plasma [β2-microglobulin] was positively correlated with disease severity. The results indicate that monocytes are activated by contact with activated endothelium in HAM. Using β2-microglobulin and Calgranulin B alone we derive a diagnostic algorithm that correctly classified the disease status (presence or absence of HAM) in 81% of HTLV-1-infected subjects in the cohort.
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影响因子：
6.5
作者：
Niederkofler, EE;Tubbs, KA;Nelson, RW
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FAHEY, JL;TAYLOR, JMG;GIORGI, JV
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GIORGI, JV
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SORG, C
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作者：
Asquith B;Mosley AJ;Heaps A;Tanaka Y;Taylor GP;McLean AR;Bangham CR
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