Pang Ronald T K, Poon Terence C W, Chan K C Allen, Lee Nelson L S, Chiu Rossa W K, Tong Yu-Kwan, Wong Ronald M Y, Chim Stephen S C, Ngai Sai M, Sung Joseph J Y, Lo Y M Dennis
Centre for Emerging Infectious Diseases, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong SAR.
Clin Chem. 2006 Mar;52(3):421-9. doi: 10.1373/clinchem.2005.061689. Epub 2006 Jan 19.
Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a new coronavirus strain, SARS-CoV. Specific proteomic patterns might be present in serum in response to the infection and could be useful for early detection of the disease.
Using surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology, we profiled and compared serum proteins of 39 patients with early-stage SARS infection and 39 non-SARS patients who were suspected cases during the SARS outbreak period. Proteomic patterns associated with SARS were identified by bioinformatic and biostatistical analyses. Features of interest were then purified and identified by tandem mass spectrometry.
Twenty proteomic features were significantly different between the 2 groups. Fifteen were increased in the SARS group, and 5 were decreased. Their concentrations were correlated with 2 or more clinical and/or biochemical variables. Two were correlated with the SARS-CoV viral load. Hierarchical clustering analysis showed that a majority of the SARS patients (95%) had similar serum proteomic profiles and identified 2 subgroups with poor prognosis. ROC curve analysis identified individual features as potential biomarkers for SARS diagnosis (areas under ROC curves, 0.733-0.995). ROC curve areas were largest for an N-terminal fragment of complement C3c alpha chain (m/z 28 119) and an internal fragment of fibrinogen alpha-E chain (m/z 5908). Immunoglobulin kappa light chain (m/z 24 505) positively correlated with viral load.
Specific proteomic fingerprints in the sera of adult SARS patients could be used to identify SARS cases early during onset with high specificity and sensitivity.
严重急性呼吸综合征（SARS）是一种由新型冠状病毒SARS-CoV引起的新发传染病。感染后血清中可能会出现特定的蛋白质组学模式，这可能有助于疾病的早期检测。
我们使用表面增强激光解吸/电离（SELDI）蛋白质芯片技术，对39例早期SARS感染患者和39例在SARS爆发期间被怀疑为病例的非SARS患者的血清蛋白质进行了分析和比较。通过生物信息学和生物统计学分析确定了与SARS相关的蛋白质组学模式。然后通过串联质谱对感兴趣的特征进行纯化和鉴定。
两组之间有20种蛋白质组学特征存在显著差异。SARS组中有15种增加，5种减少。它们的浓度与2个或更多临床和/或生化变量相关。其中2种与SARS-CoV病毒载量相关。层次聚类分析表明，大多数SARS患者（95%）具有相似的血清蛋白质组学谱，并确定了2个预后不良的亚组。ROC曲线分析确定了个体特征作为SARS诊断的潜在生物标志物（ROC曲线下面积，0.733 - 0.995）。补体C3cα链的N端片段（m/z 28119）和纤维蛋白原α-E链的内部片段（m/z 5908）的ROC曲线面积最大。免疫球蛋白κ轻链（m/z 24505）与病毒载量呈正相关。
成年SARS患者血清中的特定蛋白质组学指纹可用于在发病早期以高特异性和敏感性识别SARS病例。
