Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou 510515, China.
J Hepatol. 2012 Apr;56(4):775-81. doi: 10.1016/j.jhep.2011.10.020. Epub 2011 Dec 13.
BACKGROUND & AIMS: Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood.
Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-positive chronic hepatitis B (CHB) patients undergoing telbivudine treatment. The findings were validated in 103 patients from a separate clinical trial of telbivudine. A complete response to telbivudine was defined as having both HBeAg seroconversion and serum HBV-DNA level <300 copies/ml by treatment week 52. The proportions of T-cells producing IL-21 and/or expressing programmed death 1 (PD-1) in peripheral blood mononuclear cells were assessed longitudinally during treatment by intracellular cytokine staining and flow cytometry.
Median serum IL-21 levels at treatment week 12 were significantly higher in patients who did achieve vs. patients who did not achieve a complete response in both the initial (128.4 vs. 69.2 pg/ml, p=0.003) and the validation (142.2 vs. 89.9 pg/ml, p=0.004) trials. Serum levels of IL-21 (p=0.005) or HBV-DNA (p=0.003) levels at treatment week 12 independently predicted HBeAg seroconversion in the first year of treatment. The decrease in PD-1 expression on CD4(+) and CD8(+) T cells during the first 12 weeks on telbivudine treatment was not correlated with changes in IL-21 concentrations.
Serum IL-21 levels may be a biomarker for HBeAg seroconversion, and may contribute to individualization of antiviral therapy in HBeAg-positive CHB. IL-21 may also have a role in immunotherapy for CHB.
白细胞介素-21（IL-21）可刺激 T 细胞和 B 细胞反应，并在控制慢性病毒感染中发挥作用。IL-21 在慢性乙型肝炎病毒（HBV）感染中的作用尚不清楚。
采用酶联免疫吸附法检测 75 例接受替比夫定治疗的 HBeAg 阳性慢性乙型肝炎（CHB）患者的血清 IL-21 水平，并在替比夫定的另一项临床试验中对 103 例患者进行了验证。替比夫定的完全应答定义为治疗第 52 周时 HBeAg 血清学转换和血清 HBV-DNA 水平<300 拷贝/ml。通过细胞内细胞因子染色和流式细胞术，在治疗期间纵向评估外周血单个核细胞中产生 IL-21 和/或表达程序性死亡 1（PD-1）的 T 细胞的比例。
在最初（128.4 与 69.2 pg/ml，p=0.003）和验证（142.2 与 89.9 pg/ml，p=0.004）试验中，治疗第 12 周时达到完全应答的患者的血清 IL-21 水平中位数明显高于未达到完全应答的患者。治疗第 12 周时血清 IL-21（p=0.005）或 HBV-DNA（p=0.003）水平可独立预测治疗第一年的 HBeAg 血清学转换。替比夫定治疗前 12 周内 CD4+和 CD8+T 细胞上 PD-1 表达的降低与 IL-21 浓度的变化无关。
血清 IL-21 水平可能是 HBeAg 血清学转换的生物标志物，并可能有助于 HBeAg 阳性 CHB 的抗病毒个体化治疗。IL-21 也可能在 CHB 的免疫治疗中发挥作用。
