Cytokine expression patterns associated with systemic adverse events following smallpox immunization
Cytokine expression patterns associated with systemic adverse events following smallpox immunization
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DOI：
10.1086/505503
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发表时间：
2006-08-15
影响因子：
6.4
通讯作者：
Crowe, James E., Jr.
中科院分区：
文献类型：
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作者：
McKinney, Brett A.;Reif, David M.;Crowe, James E., Jr.
牛痘病毒在相当数量的疫苗接种者中是反应原性的，最常见的不良事件是发热、淋巴结病和皮疹。虽然接种是在皮肤中进行的，但这些不良事件表明存在强烈的全身炎症反应。为了阐明系统性不良事件的细胞因子应答特征，我们使用蛋白质微阵列技术精确定量接种Aventis Pasteur天花疫苗之前和之后1周的疫苗接受者中的108种血清细胞因子和趋化因子。我们研究了74名接种疫苗后的个体，其中22人发生了全身性不良事件，52人没有。根据机器学习方法和统计程序委员会的投票选择与不良事件最相关的可溶性因素，并使用所选细胞因子构建最终决策树模型。在蛋白质表达变化的基础上，我们确定了6种细胞因子，根据不良事件状态准确区分个体：粒细胞集落刺激因子，干细胞因子，干扰素-γ（CXCL 9）诱导的单核因子，细胞间粘附分子-1，eotaxin和金属蛋白酶组织抑制剂-2。这种细胞因子特征是特定炎症反应途径的特征，并表明成纤维细胞分泌细胞因子在全身不良事件中起核心作用。
Vaccinia virus is reactogenic in a significant number of vaccinees, with the most common adverse events being fever, lymphadenopathy, and rash. Although the inoculation is given in the skin, these adverse events suggest a robust systemic inflammatory response. To elucidate the cytokine response signature of systemic adverse events, we used a protein microarray technique to precisely quantitate 108 serum cytokines and chemokines in vaccine recipients before and 1 week after primary immunization with Aventis Pasteur smallpox vaccine. We studied 74 individuals after vaccination, of whom 22 experienced a systemic adverse event and 52 did not. The soluble factors most associated with adverse events were selected on the basis of voting among a committee of machine-learning methods and statistical procedures, and the selected cytokines were used to build a final decision-tree model. On the basis of changes in protein expression, we identified 6 cytokines that accurately discriminate between individuals on the basis of adverse event status: granulocyte colony-stimulating factor, stem cell factor, monokine induced by interferon-gamma (CXCL9), intercellular adhesion molecule-1, eotaxin, and tissue inhibitor of metalloproteinases-2. This cytokine signature is characteristic of particular inflammatory response pathways and suggests that the secretion of cytokines by fibroblasts plays a central role in systemic adverse events.