Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Gastroenterology. 2010 Jan;138(1):165-72.e1-3. doi: 10.1053/j.gastro.2009.09.018. Epub 2009 Sep 24.
BACKGROUND & AIMS: This prospective cohort study aimed to determine the effect of cytokines on spontaneous hepatitis B e antigen (HBeAg) seroconversion in patients with chronic hepatitis B virus (HBV) infection.
Polymorphisms in interleukin (IL)-2, IL-4, IL-10, IL-12beta, and interferon-gamma were evaluated in 288 HBeAg-positive chronic HBV patients (median initial age, 8.6 years; median follow-up duration, 19.3 years). Serum cytokine levels were determined in 154 subjects (53.5%) before and after HBeAg seroconversion by enzyme-linked immunosorbent assay analysis. Peripheral blood mononuclear cells (PBMC) were isolated from patients with chronic HBV infection and stimulated with HBV core antigen (HBcAg); data on cytokine genotypes and phenotypes were compared.
The IL-10-1082 G/G and IL-12beta -10993C/G genotypes predicted early, spontaneous HBeAg seroconversion (hazard ratio [HRs] = 3.43 and 1.54; P < .001, and P < .004, respectively), based on multivariate survival analysis. The IL-10 -1082 G/G genotype was associated with higher serum levels of IL-10 and IL-12; the IL-12beta -10993 C/G genotype predicted higher levels of IL-12 secretion by PBMC after in vitro HBcAg stimulation (P = .04). Higher levels of serum IL-12 (>45 pg/mL) and IL-10 (>70 pg/mL) were associated with early, spontaneous HBeAg seroconversion (HR = 1.52 and 1.48; P = .04 and .02, respectively).
The IL-10-1082 G/G is associated with higher serum IL-10 and IL-12 levels and IL-12beta -10993 C/G is associated with increased secretion of IL-12 in response to HBcAg stimulation of PBMC. Both genotypes are associated with early, spontaneous HBeAg seroconversion. Higher serum levels of IL-10 and IL-12 in HBeAg-positive patients are correlated with early, spontaneous HBeAg seroconversion.
本前瞻性队列研究旨在确定细胞因子对慢性乙型肝炎病毒（HBV）感染患者自发乙型肝炎 e 抗原（HBeAg）血清学转换的影响。
在 288 例 HBeAg 阳性慢性 HBV 患者（中位初始年龄 8.6 岁；中位随访时间 19.3 年）中评估白细胞介素（IL）-2、IL-4、IL-10、IL-12β和干扰素-γ的多态性。通过酶联免疫吸附试验分析，在 154 例（53.5%）HBeAg 血清学转换前后测定血清细胞因子水平。从慢性 HBV 感染患者中分离外周血单个核细胞（PBMC），并用乙型肝炎核心抗原（HBcAg）刺激；比较细胞因子基因型和表型的数据。
基于多变量生存分析，IL-10-1082 G/G 和 IL-12β-10993C/G 基因型预测了早期、自发性 HBeAg 血清学转换（风险比[HR]分别为 3.43 和 1.54；P<0.001 和 P<0.004）。IL-10-1082 G/G 基因型与血清中更高水平的 IL-10 和 IL-12 相关；IL-12β-10993 C/G 基因型预测 PBMC 体外 HBcAg 刺激后更高水平的 IL-12 分泌（P=0.04）。更高水平的血清 IL-12（>45 pg/mL）和 IL-10（>70 pg/mL）与早期、自发性 HBeAg 血清学转换相关（HR 分别为 1.52 和 1.48；P=0.04 和 0.02）。
IL-10-1082 G/G 与更高水平的血清 IL-10 和 IL-12 相关，IL-12β-10993 C/G 与 PBMC 对 HBcAg 刺激时 IL-12 分泌增加相关。这两种基因型均与早期、自发性 HBeAg 血清学转换相关。HBeAg 阳性患者血清中更高水平的 IL-10 和 IL-12 与早期、自发性 HBeAg 血清学转换相关。
