Peking University People's Hospital, Peking University Hepatology Institute, Beijing, 100044, China.
Sci China Life Sci. 2011 Jan;54(1):39-47. doi: 10.1007/s11427-010-4111-4. Epub 2011 Jan 21.
The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predicting hepatitis B e antigen (HBeAg) seroconversion in these patients during IFN therapy. Two groups of patients were enrolled: training and validation. In the training group, 2-DE experiments and subsequent identification of altered levels of proteins showed that α-2-HS-glycoprotein, leucine-rich α-2-glycoprotein, and haptoglobin were significantly upregulated as compared with baseline levels in the HBeAg seroconversion group, whereas apolipoprotein C-III precursor, leucine-rich α-2-glycoprotein, and α-albumin were downregulated in the non-seroconversion group. For patients with HBeAg seroconversion in the training group, Western blot analyses showed that α-2-HS-glycoprotein levels in 75% of patients were significantly upregulated at the end of the treatment as compared with baseline levels. Subsequent experiments in the validation group showed that α-2-HS-glycoprotein levels were significantly increased at week 4 in 83.33% of patients in the HBeAg seroconversion group. Dynamic changes in the serum level of α-2-HS-glycoprotein may be a potential early marker for predicting HBeAg seroconversion during IFN treatment for CHB.
干扰素(IFN)的疗效在约 1/3 的慢性乙型肝炎(CHB)患者中有限。我们使用基于二维电泳(2-DE)的蛋白质组学策略来鉴定在 IFN 治疗期间这些患者中预测乙型肝炎 e 抗原(HBeAg)血清学转换的潜在血清标志物。招募了两组患者:训练组和验证组。在训练组中,2-DE 实验和随后鉴定的蛋白水平变化表明,与 HBeAg 血清学转换组的基线水平相比,α-2-HS-糖蛋白、富含亮氨酸的α-2-糖蛋白和触珠蛋白显着上调,而载脂蛋白 C-III 前体、富含亮氨酸的α-2-糖蛋白和α-白蛋白在未发生血清学转换的组中下调。对于训练组中 HBeAg 血清学转换的患者,Western blot 分析显示,75%的患者在治疗结束时α-2-HS-糖蛋白水平与基线水平相比显着上调。验证组的后续实验表明,在 HBeAg 血清学转换组中,83.33%的患者在第 4 周时α-2-HS-糖蛋白水平显着增加。α-2-HS-糖蛋白血清水平的动态变化可能是预测 CHB 患者 IFN 治疗中 HBeAg 血清学转换的潜在早期标志物。