原发性胆汁性胆管炎患者肝脏雌激素受体与外周血细胞因子及自身抗体的相关性分析

Correlation analysis of estrogen receptor, cytokines, and autoantibodies in liver of patients with primary biliary cholangitis

摘要:

目的 探讨原发性胆汁性胆管炎（PBC）患者肝脏雌激素受体（ER-α）与外周血Th1、Th2细胞因子及自身抗体的相关性。方法 选择2015年12月—2017年12月南京市第二医院收治的PBC患者62例（PBC组）、自身免疫性肝炎患者60例（AIH组）及同期门诊体检健康者50例（对照组）为研究对象。酶联免疫吸附试验（ELISA）检测受试者外周血Th1细胞因子［干扰素（INF-γ）、白细胞介素-2（IL-2）］、Th2细胞因子［白细胞介素-4（IL-4）、白细胞介素-10（IL-10）］的质量浓度和自身抗体（AMA-M2、抗LKM-1抗体、抗LC1抗体、抗GP210抗体、抗SLA抗体、抗SP100抗体）的阳性情况。免疫组织化学（IHC）检测PBC组、AIH组肝组织中ER-α表达情况。Pearson法分析ER-α与Th1/Th2细胞因子、自身抗体的相关性。结果 3组INF-γ、IL-2、IL-4、IL-10质量浓度的比较，差异有统计学意义（P <0.05），PBC组均高于AIH组（P <0.05），AIH组均高于对照组（P <0.05）。PBC组和AIH组ER-α的阳性表达比较，差异有统计学意义（P <0.05），PBC组以高表达为主（53.23%），AIH组以低表达为主（75.00%）。PBC组ER-α与血清AMA-M2、抗GP210抗体、抗SP100抗体阳性率呈正相关（r =0.530、0.602和0.652，P <0.05），与外周血INF-γ、IL-2、IL-4、IL-10呈正相关（r =0.615、0.593、0.558和0.601，均P <0.05），与抗LKM-1抗体、抗LC1抗体、抗SLA抗体无关（r =0.135、0.068和0.095，均P >0.05）。结论 PBC患者肝组织中ER-α阳性表达升高，INF-γ、IL-2、IL-4、IL-10质量浓度升高，AMA-M2、抗LKM-1抗体、抗LC1抗体、抗GP210抗体、抗SP100抗体阳性表达升高，ER-α与INF-γ、IL-2、IL-4、IL-10呈正相关，ER-α与AMA-M2、抗GP210抗体、抗SP100抗体表达呈正相关。ER-α阳性表达可能是PBC发病原因之一。

Abstract:

Objective To investigate the correlation between liver estrogen receptor (ER-alpha) and Th1/Th2 cytokines and autoantibodies in peripheral blood of patients with primary biliary cirrhosis (PBC).Methods From December 2015 to December 2017, 62 patients with PBC (PBC group), 60 patients with autoimmune hepatitis (AIH group) and 50 healthy outpatients (control group) were selected as subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of Th1 cytokines [interferon-gamma, interleukin-2 (IL-2)], Th2 cytokines [interleukin-4 (IL-4), interleukin-10 (IL-10)], autoantibodies (MA-M2, anti-LKM-l, anti-LCI, anti-GP210, anti-SLA, anti-SPl00). Immunohistochemical staining (IHC) was used to detect the expression of ER- alpha in liver tissue of PBC group and AIH group. Bivariate correlation was used to analyze the correlation between ER- alpha and Th1/Th2 cytokines and autoantibodies.Result Comparison of the levels of INF-γ, IL-2, IL-4, and IL-10 in the three groups showed statistically significant differences (P < 0.05) after analysis of variance. The levels of IL-10 and IL-10 were higher than those in AIH group (P < 0.05), and the levels of NF-γ, IL-2, IL-4 and IL-10 in AIH group were higher than those in control group (P < 0.05). The expression of ER-alpha was mainly high in PBC group (53.23%) and low in AIH group (75.00%). There was significant difference between the two groups (P < 0.05). ER-alpha in PBC group was positively correlated with serum MA-M2, anti-GP210 antibody and anti-SPl00 antibody (r = 0.530, 0.602, and 0.652, P < 0.05), and positively correlated with peripheral blood INF-γ, IL-2, IL-4 and IL-10 (r = 0.615, 0.593, 0.558, and 0.601, P < 0.05), but not with anti-LKM-l antibody, anti-LCI antibody and anti-SLA antibody (r = 0.135, 0.068, and 0.095, P > 0.05).Conclusion The positive rates of ER-alpha in liver tissue, Th1/Th2 cytokines and autoantibodies in peripheral blood of PBC patients are significantly increased. The expression of ER-alpha is significantly correlated with Th1/Th2 cytokines and autoantibodies in peripheral blood. The positive expression of ER-alpha may be one of the causes of PBC.