Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases
Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases
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DOI：
10.1007/s00535-010-0199-3
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发表时间：
2010-07-01
影响因子：
6.3
通讯作者：
Okazaki, Kazuichi
中科院分区：
文献类型：
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作者：
Koyabu, Masanori;Uchida, Kazushige;Okazaki, Kazuichi
自身免疫性胰腺炎(AIP)患者的特点是血清免疫球蛋白G4(IgG4)水平升高，受累器官中有大量IgG4阳性浆细胞浸润。胰外病变最常见的受累器官是胆管，表现为硬化性胆管炎。然而，IgG4在IgG4相关SC(IgG4-SC)发生发展中的作用尚不清楚。为了阐明IgG4在IgG4-SC中的作用，我们对胆管进行了免疫组织化学分析，比较了IgG4-SC、原发性硬化性胆管炎(PSC)、自身免疫性肝炎(AIH)和原发性胆汁性肝硬变(PBC)患者的肝活检标本的实验室和免疫组织化学结果。首先用抗IgG1、抗IgG4和抗Foxp3(叉头盒P3)抗体染色，检测IgG4、IgG1和Foxp3阳性细胞与浸润性单个核细胞(IgG4/Mono、IgG1/Mono、Foxp3/Mono)的比值，发现IgG4/IgG1阳性浆细胞比例在PSC、AIH和PBC中显著高于PSC、AIH和PBC。PBC患者的Foxp3/Mono比值明显高于IgG4-SC和PSC患者。在IgG4-SC患者中，Foxp3阳性细胞数与IgG4阳性细胞数显著相关，而在其他患者组中无相关性，肝脏中IgG4/IgG1比值可作为鉴别诊断IgG4-SC和PSC的有用指标。在IgG4-SC中，调节性T细胞(Tregs)的大量浸润可能会影响B细胞向产生IgG4的浆细胞的转换，并且在IgG4-SC和其他肝病(PSC、AIH和PBC)中，Tregs的功能可能不同。
Patients with autoimmune pancreatitis (AIP) characteristically show elevated serum levels of immunoglobulin G4 (IgG4) and abundant infiltration of IgG4-positive plasmacytes in the involved organs. The most common involved organ showing extrapancreatic lesions is the bile duct, which exhibits sclerosing cholangitis (SC). However, the role of IgG4 in the development of IgG4-related SC (IgG4-SC) remains unclear. To clarify the role of IgG4 in IgG4-SC, we have performed an immunohistochemical analysis of the bile duct.Laboratory and immunohistochemical findings of liver biopsy specimens obtained from patients with IgG4-SC, primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and primary biliary cirrhosis (PBC) were compared. The biopsy specimens were first stained with anti-IgG1, anti-IgG4, and anti-Foxp3 (forkhead box P3) antibodies, and the ratio of IgG4-, IgG1-, and Foxp3-positive cells, respectively, to infiltrated mononuclear cells (IgG4/Mono, IgG1/Mono, Foxp3/Mono) was assessed.The ratio of IgG4/IgG1-positive plasma cells was significantly higher in specimens obtained from patients with IgG4-SC than in those from patients with PSC, AIH, and PBC. The Foxp3/Mono ratio in patients with PBC was significantly higher than that in patients with IgG4-SC and PSC. In patients with IgG4-SC, the number of Foxp3-positive cells was significantly correlated with the number of IgG4-positive cells; in the other patient groups, there was no correlation.The IgG4/IgG1 ratio in the liver may be a useful marker for differential diagnosis of IgG4-SC and PSC. In IgG4-SC, abundant infiltration of regulatory T cells (Tregs) may affect the switching of B cells to IgG4-producing plasmacytes, and there is a possibility that the function of Tregs is different in IgG4-SC and other liver diseases (PSC, AIH, and PBC).