Liu Wen Ting, Jing Ying Ying, Han Zhi Peng, Li Xiao Ning, Liu Yan, Lai Fo Bao, Li Rong, Zhao Qiu-Dong, Wu Meng-Chao, Wei Li-Xin
Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
Health Quarantine and Supervision Department, Fujian Entry-Exit Inspectation & Quarantine Bureau of P.R.C., Fuzhou, China.
PLoS One. 2015 Mar 31;10(3):e0122739. doi: 10.1371/journal.pone.0122739. eCollection 2015.
Hyperimmunoglobulinemia is frequently observed in patients with chronic liver diseases. However, the exact mechanism underlying the high level of antibody formation is not fully understood. In our study, we provide evidence for the functional role of the liver and the stimulation of plasma cell proliferation in hyperimmunoglobulinemia. We collected sera from patients with chronic liver diseases, and the level of serum immunoglobulins in patients was examined; this was also investigated in animal models of liver cirrhosis and hepatocellular carcinoma. An end-to-side microsurgical portacaval shunt was used to mimic liver dysfunction in rats. We used portal vein serum and inferior vena cava serum to immunize healthy rats and mice in order to confirm the function of the healthy liver in disposing of antigens and endotoxins from the gut. For the analysis of the state of plasma cell activation, plasma cells from mice were stained with PE-conjugated anti-CD138 and FITC-conjugated anti-BrdU for flow cytometry analysis. Hyperimmunoglobulinemia was observed both in patients with chronic liver diseases and in related animal models, and high plasma LPS levels were also observed. There was a significant increase in the activation and proliferation of plasma cell in mice immunized with antigens or LPS-positive serum compared with controls that were immunized with antigens and LPS-negative serum. We confirmed that the healthy liver plays an important role in disposing of antigens and endotoxins derived from the gut. Hyperimmunoglobulinemia in chronic liver diseases mainly arises due to the collateral circulation secondary to portal hypertension, gut antigens and endotoxins that bypass the liver and reach the antibody-producing cells.
高免疫球蛋白血症在慢性肝病患者中经常可见。然而，抗体形成水平升高背后的确切机制尚未完全明确。在我们的研究中，我们为肝脏在高免疫球蛋白血症中的功能作用以及浆细胞增殖的刺激提供了证据。我们收集了慢性肝病患者的血清，并检测了患者血清免疫球蛋白水平；在肝硬化和肝细胞癌动物模型中也进行了此项研究。采用端侧显微外科门腔分流术模拟大鼠肝功能障碍。我们使用门静脉血清和下腔静脉血清免疫健康大鼠和小鼠，以证实健康肝脏在清除来自肠道的抗原和内毒素方面的功能。为了分析浆细胞激活状态，用PE偶联的抗CD138和FITC偶联的抗BrdU对小鼠的浆细胞进行染色，用于流式细胞术分析。在慢性肝病患者和相关动物模型中均观察到高免疫球蛋白血症，同时也观察到血浆LPS水平升高。与用抗原和LPS阴性血清免疫的对照组相比，用抗原或LPS阳性血清免疫的小鼠浆细胞的激活和增殖显著增加。我们证实健康肝脏在清除来自肠道的抗原和内毒素方面发挥重要作用。慢性肝病中的高免疫球蛋白血症主要是由于门静脉高压继发的侧支循环、绕过肝脏并到达抗体产生细胞的肠道抗原和内毒素所致。
