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Liver Res. 2018 Mar;2(1):52-59. doi: 10.1016/j.livres.2018.02.001. Epub 2018 Feb 22.

Levels of circulating follicular helper T cells, T helper 1 cells, and the prognostic significance of soluble form of CD40 ligand on survival in patients with alcoholic cirrhosis.

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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.
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Physiology and Neurobiology, and the Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA.
Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT, USA.
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA.



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. In vitro 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 (P<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 (P<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.


Alcoholic cirrhosis (AC); Alcoholic liver disease (ALD); Circulating follicular helper T (cTFH) cells; Follicular helper T (TFH) cells; Soluble form of CD40 ligand (sCD40L); T helper 1 (Th1)

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