Ho Cheng-Hsun, Chien Rong-Nan, Cheng Pin-Nan, Liu Cheng-Kun, Su Chih-Sheng, Wu I-Chin, Liu Wen-Chun, Chen Shu-Hui, Chang Ting-Tsung
Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, Taiwan.
Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan.
Antiviral Res. 2014 Nov;111:121-8. doi: 10.1016/j.antiviral.2014.09.011. Epub 2014 Sep 28.
Aberrant serum IgG N-glycome has been demonstrated in various autoimmune diseases and viral infections. However, the correlation between serum IgG N-glycome and cytokine is unclear. In addition, the clinical relevance of IgG glycosylation and cytokine changes in the treatment outcome of chronic hepatitis B (CHB) has never been assessed. One hundred and three treatment-naive patients with CHB and 101 healthy controls were enrolled in this retrospective cohort study. Serum samples in patients before and after 48weeks of entecavir treatment were collected. In-gel trypsinized serum IgG heavy chain was analyzed using liquid chromatography-tandem mass spectrometry. Selected ion chromatograms corresponding to 10 N-glycoforms on asparagine 297 were individually extracted to calculate the percentage of each glycoforms. Serum cytokine profiles were examined using enzyme-linked immunosorbent assay. Forty-eight weeks of entecavir treatment resulted in decreases in galactose-deficient (total G0) IgG and transforming growth factor (TGF)-β1 levels (both P<0.001) in patients with CHB. The changes in TGF-β1 (ΔTGF-β1) and IgG total G0 (Δtotal G0) levels during treatment were significantly correlated (r=0.403, P<0.001). Furthermore, higher levels of Δtotal G0 (P<0.01) and ΔTGF-β1 (P<0.001) were found in hepatitis B virus e antigen (HBeAg)-positive patients than in HBeAg-negative patients and were also found in patients with HBeAg seroconversion at week 48. The area under the receiver operating characteristic (ROC) curves for Δtotal G0 and ΔTGF-β1 to discriminate a week-48 HBeAg seroconversion were 0.835 and 0.830, respectively. These results suggested a correlation between serum cytokine and IgG N-glycome and its effect on the outcome of entecavir treatment in patients with CHB.
异常血清IgG N-聚糖已在多种自身免疫性疾病和病毒感染中得到证实。然而，血清IgG N-聚糖与细胞因子之间的相关性尚不清楚。此外，IgG糖基化和细胞因子变化在慢性乙型肝炎（CHB）治疗结局中的临床相关性从未得到评估。本回顾性队列研究纳入了103例未经治疗的CHB患者和101例健康对照。收集恩替卡韦治疗48周前后患者的血清样本。使用液相色谱-串联质谱分析凝胶内胰蛋白酶消化后的血清IgG重链。分别提取对应于天冬酰胺297上10种N-糖型的选择离子色谱图，以计算每种糖型的百分比。使用酶联免疫吸附测定法检测血清细胞因子谱。恩替卡韦治疗48周导致CHB患者中半乳糖缺乏（总G0）IgG和转化生长因子（TGF）-β1水平降低（均P<0.001）。治疗期间TGF-β1（ΔTGF-β1）和IgG总G0（Δ总G0）水平的变化显著相关（r=0.403，P<0.001）。此外，乙型肝炎病毒e抗原（HBeAg）阳性患者的Δ总G0（P<0.01）和ΔTGF-β1（P<0.001）水平高于HBeAg阴性患者，并且在第48周发生HBeAg血清学转换的患者中也发现了更高水平。用于区分第48周HBeAg血清学转换的Δ总G0和ΔTGF-β1的受试者操作特征（ROC）曲线下面积分别为0.835和0.830。这些结果提示血清细胞因子与IgG N-聚糖之间存在相关性及其对CHB患者恩替卡韦治疗结局的影响。
