Hollister Kristin, Kusumanchi Praveen, Ross Ruth Ann, Chandler Kristina, Oshodi AdePeju, Heathers Laura, Teagarden Sean, Wang Li, Dent Alexander L, Liangpunsakul Suthat
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Liver Res. 2018 Mar;2(1):52-59. doi: 10.1016/j.livres.2018.02.001. Epub 2018 Feb 22.
Excessive drinkers (ED) and patients with alcoholic liver disease (ALD) are several times more susceptible to bacterial and viral infections and have a decrease in antibody responses to vaccinations. Follicular helper T (TFH) cells are essential to select B cells in the germinal center and to produce antibodies. TFH cells express both a membrane-associated and a soluble form of CD40 ligand (sCD40L); in which the latter form is released to circulation upon T cell activation. The effect of alcohol on TFH cells has not been studied.
The goals of this study are to determine the levels of TFH and T helper 1 (Th1) cells in ED and those with alcoholic cirrhosis (AC) when compared to healthy controls and to determine the prognostic significance of sCD40L in a cohort of patients with AC.
Controls, ED, and those with AC were enrolled. Baseline demographic, laboratory tests, and peripheral blood mononuclear cells (PBMCs) were isolated and assessed via flow cytometry for TFH cells. study was performed to determine the ability of PBMCs to secrete interferon (IFN)-γ upon stimulation. Serum sCD40L were also determined and its prognostic significance was tested in a cohort of AC patients.
The levels of circulating TFH (cTFH) cells were significantly lower in peripheral blood of subjects with ED and AC compared to controls (<0.05). IFN-γ secretion from PBMCs upon stimulation was also lower in ED and those with cirrhosis. Serum sCD40L was significantly lower in ED and AC when compared to that in controls (<0.0005). Its level was an independent predictor of mortality.
Patients with AC had significantly lower level of cTFH and sCD40L. The level of sCD40L was an independent predictor of mortality in these patients.
酗酒者（ED）和酒精性肝病（ALD）患者比正常人更容易受到细菌和病毒感染，并且对疫苗接种的抗体反应降低。滤泡辅助性T（TFH）细胞对于在生发中心选择B细胞和产生抗体至关重要。TFH细胞表达膜相关形式和可溶性形式的CD40配体（sCD40L）；后者在T细胞激活后释放到循环中。酒精对TFH细胞的影响尚未得到研究。
本研究的目的是确定与健康对照相比，酗酒者和酒精性肝硬化（AC）患者中TFH和辅助性T1（Th1）细胞的水平，并确定sCD40L在一组AC患者中的预后意义。
纳入对照、酗酒者和AC患者。收集基线人口统计学、实验室检查数据，并分离外周血单个核细胞（PBMC），通过流式细胞术评估TFH细胞。进行一项研究以确定PBMC在刺激后分泌干扰素（IFN）-γ的能力。还测定了血清sCD40L，并在一组AC患者中测试了其预后意义。
与对照组相比，酗酒者和AC患者外周血中循环TFH（cTFH）细胞水平显著降低（<0.05）。酗酒者和肝硬化患者PBMC在刺激后IFN-γ分泌也较低。与对照组相比，酗酒者和AC患者血清sCD40L显著降低（<0.0005）。其水平是死亡率的独立预测因子。
AC患者的cTFH和sCD40L水平显著降低。sCD40L水平是这些患者死亡率的独立预测因子。
