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
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 a...
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| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2018-03-01
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| Series: | Liver Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2542568418000028 |
| _version_ | 1819283229442572288 |
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| author | Kristin Hollister Praveen Kusumanchi Ruth Ann Ross Kristina Chandler AdePeju Oshodi Laura Heathers Sean Teagarden Li Wang Alexander L. Dent Suthat Liangpunsakul |
| author_facet | Kristin Hollister Praveen Kusumanchi Ruth Ann Ross Kristina Chandler AdePeju Oshodi Laura Heathers Sean Teagarden Li Wang Alexander L. Dent Suthat Liangpunsakul |
| author_sort | Kristin Hollister |
| collection | DOAJ |
| description | 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. Keywords: Follicular helper T (TFH) cells, Circulating follicular helper T (cTFH) cells, T helper 1 (Th1), Soluble form of CD40 ligand (sCD40L), Alcoholic liver disease (ALD), Alcoholic cirrhosis (AC) |
| first_indexed | 2024-12-24T01:28:10Z |
| format | Article |
| id | doaj.art-4c1c3d4badf94876a7624f72505c2918 |
| institution | Directory Open Access Journal |
| issn | 2542-5684 |
| language | English |
| last_indexed | 2024-12-24T01:28:10Z |
| publishDate | 2018-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Liver Research |
| spelling | doaj.art-4c1c3d4badf94876a7624f72505c29182022-12-21T17:22:26ZengKeAi Communications Co., Ltd.Liver Research2542-56842018-03-01215259Levels 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 cirrhosisKristin Hollister0Praveen Kusumanchi1Ruth Ann Ross2Kristina Chandler3AdePeju Oshodi4Laura Heathers5Sean Teagarden6Li Wang7Alexander L. Dent8Suthat Liangpunsakul9Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USADivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USADivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USADivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USADivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USADivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Physiology and Neurobiology, 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, ChinaDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA; Corresponding authors. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA (A. L. Dent). Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA (S. Liangpunsakul).Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA; Corresponding authors. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA (A. L. Dent). Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA (S. Liangpunsakul).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. Keywords: Follicular helper T (TFH) cells, Circulating follicular helper T (cTFH) cells, T helper 1 (Th1), Soluble form of CD40 ligand (sCD40L), Alcoholic liver disease (ALD), Alcoholic cirrhosis (AC)http://www.sciencedirect.com/science/article/pii/S2542568418000028 |
| spellingShingle | Kristin Hollister Praveen Kusumanchi Ruth Ann Ross Kristina Chandler AdePeju Oshodi Laura Heathers Sean Teagarden Li Wang Alexander L. Dent Suthat Liangpunsakul 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 Liver Research |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://www.sciencedirect.com/science/article/pii/S2542568418000028 |
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