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

Kristin Hollister, Praveen Kusumanchi, Ruth Ann Ross, Kristina Chandler, Ade Peju Oshodi, Laura Heathers, Sean Teagarden, Li Wang, Alexander L. Dent, Suthat Liangpunsakul

Research output: Contribution to journalArticle

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Abstract

Background: 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. Objectives: 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. Methods: 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)-ɣ upon stimulation. Serum sCD40L was also determined and its prognostic significance was tested in a cohort of AC patients. Results: 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-ɣ 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. Conclusions: Patients with AC had significantly lower level of cTFH and sCD40L. The level of sCD40L was an independent predictor of mortality in these patients.

Original languageEnglish (US)
Pages (from-to)52-59
Number of pages8
JournalLiver Research
Volume2
Issue number1
DOIs
StatePublished - Mar 2018

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Alcoholic Liver Cirrhosis
CD40 Ligand
Helper-Inducer T-Lymphocytes
Survival
Blood Cells
Interferons
Alcoholic Liver Diseases
Th1 Cells
Germinal Center
Mortality
Virus Diseases
Serum
Bacterial Infections
Antibody Formation
Flow Cytometry
Vaccination
Fibrosis
B-Lymphocytes
Alcohols
Demography

Keywords

  • 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)

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

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. / Hollister, Kristin; Kusumanchi, Praveen; Ross, Ruth Ann; Chandler, Kristina; Oshodi, Ade Peju; Heathers, Laura; Teagarden, Sean; Wang, Li; Dent, Alexander L.; Liangpunsakul, Suthat.

In: Liver Research, Vol. 2, No. 1, 03.2018, p. 52-59.

Research output: Contribution to journalArticle

Hollister, Kristin ; Kusumanchi, Praveen ; Ross, Ruth Ann ; Chandler, Kristina ; Oshodi, Ade Peju ; Heathers, Laura ; Teagarden, Sean ; Wang, Li ; Dent, Alexander L. ; Liangpunsakul, Suthat. / 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. In: Liver Research. 2018 ; Vol. 2, No. 1. pp. 52-59.
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AU - Hollister, Kristin

AU - Kusumanchi, Praveen

AU - Ross, Ruth Ann

AU - Chandler, Kristina

AU - Oshodi, Ade Peju

AU - Heathers, Laura

AU - Teagarden, Sean

AU - Wang, Li

AU - Dent, Alexander L.

AU - Liangpunsakul, Suthat

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N2 - Background: 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. Objectives: 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. Methods: 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)-ɣ upon stimulation. Serum sCD40L was also determined and its prognostic significance was tested in a cohort of AC patients. Results: 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-ɣ 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. Conclusions: Patients with AC had significantly lower level of cTFH and sCD40L. The level of sCD40L was an independent predictor of mortality in these patients.

AB - Background: 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. Objectives: 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. Methods: 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)-ɣ upon stimulation. Serum sCD40L was also determined and its prognostic significance was tested in a cohort of AC patients. Results: 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-ɣ 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. Conclusions: Patients with AC had significantly lower level of cTFH and sCD40L. The level of sCD40L was an independent predictor of mortality in these patients.

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KW - Follicular helper T (TFH) cells

KW - Soluble form of CD40 ligand (sCD40L)

KW - T helper 1 (Th1)

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