Taneja Shikha, Sen Somdutta, Gupta Vijay K, Aggarwal Rakesh, Jameel Shahid
International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Proteome Sci. 2009 Oct 27;7:39. doi: 10.1186/1477-5956-7-39.
Hepatitis E, caused by the hepatitis E virus (HEV), is endemic to developing countries where it manifests as waterborne outbreaks and sporadic cases. Though generally self-limited with a low mortality rate, some cases progress to fulminant hepatic failure (FHF) with high mortality. With no identified predictive or diagnostic markers, the events leading to disease exacerbation are not known. Our aim is to use proteomic tools to identify biomarkers of acute and fulminant hepatitis E.
We analyzed proteins in the plasma and urine of hepatitis E patients and healthy controls by two-dimensional Differential Imaging Gel Electrophoresis (DIGE) and mass spectrometry, and identified over 30 proteins to be differentially expressed during acute hepatitis E. The levels of one plasma protein, transthyretin, and one urine protein, alpha-1-microglobulin (alpha1m), were then quantitated by enzyme immunoassay (EIA) in clinical samples from a larger group of patients and controls. The results showed decreased plasma transthyretin levels (p < 0.005) and increased urine alpha1m levels (p < 0.001) in acute hepatitis E patients, compared to healthy controls. Preliminary results also showed lower urine zinc alpha glycoprotein levels in fulminant hepatitis E compared to acute disease; this remains to be confirmed with more fulminant cases.
Our results demonstrate the utility of characterizing plasma and urine proteomes for signatures of the host response to HEV infection. We predict that plasma transthyretin and urine alpha1m could be reliable biomarkers of acute hepatitis E. Besides the utility of this approach to biomarker discovery, proteome-level changes in human biofluids would also guide towards a better understanding of host-virus interaction and disease.
戊型肝炎由戊型肝炎病毒（HEV）引起，在发展中国家呈地方性流行，表现为水源性暴发和散发病例。虽然一般为自限性疾病，死亡率较低，但部分病例会进展为暴发性肝衰竭（FHF），死亡率很高。由于尚未发现预测或诊断标志物，导致疾病恶化的事件尚不清楚。我们的目的是使用蛋白质组学工具来鉴定急性和暴发性戊型肝炎的生物标志物。
我们通过二维差异凝胶电泳（DIGE）和质谱分析了戊型肝炎患者和健康对照者血浆和尿液中的蛋白质，鉴定出30多种在急性戊型肝炎期间差异表达的蛋白质。然后通过酶免疫测定（EIA）对来自更多患者和对照的临床样本中的一种血浆蛋白转甲状腺素蛋白和一种尿液蛋白α1微球蛋白（α1m）的水平进行定量。结果显示，与健康对照相比，急性戊型肝炎患者血浆转甲状腺素蛋白水平降低（p < 0.005），尿液α1m水平升高（p < 0.001）。初步结果还显示，与急性疾病相比，暴发性戊型肝炎患者尿液锌α糖蛋白水平较低；这有待更多暴发性病例进一步证实。
我们的结果证明了对血浆和尿液蛋白质组进行表征以寻找宿主对HEV感染反应特征的实用性。我们预测血浆转甲状腺素蛋白和尿液α1m可能是急性戊型肝炎可靠的生物标志物。除了这种生物标志物发现方法的实用性外，人类生物流体中蛋白质组水平的变化也将有助于更好地理解宿主 - 病毒相互作用和疾病。
