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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

查看全文 作　　者：Kristin [1]Hollister;Praveen [2]Kusumanchi;Ruth Ann [2]Ross;Kristina [2]Chandler;AdePeju [2]Oshodi;Laura [3]Heathers;Sean [2]Teagarden;Li [4,5,6,7]Wang;Alexander [1]L.Dent;Suthat [2,8,9]Liangpunsakul 高影响力作者 机构地区：[1]Department of Microbiology and Immunology,Indiana University School of Medicine,Indianapolis,IN,USA;[2]Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine,Indianapolis,IN,USA;[3]Department of Medical and Molecular Genetics,Indiana University School of Medicine,Indianapolis,IN,USA;[4]Department of Physiology and Neurobiology,The Institute for Systems Genomics,University of Connecticut,Storrs,CT,USA;[5]Veterans Affairs Connecticut Healthcare System,West Haven,CT,USA;[6]Department of Internal Medicine,Section of Digestive Diseases,Yale University,New Haven,CT,USA;[7]School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,Zhejiang,China;[8]Department of Biochemistry and Molecular Biology,Indiana University School of Medicine,Indianapolis,IN,USA;[9]Roudebush Veterans Administration Medical Center,Indianapolis,IN,USA高影响力机构 出　　处：《Liver Research》索引2018年第2卷第1期,共8页高影响力期刊 基　　金：This work was supported by VA Merit Award 1I01BX002634,the NIH R21AA022482,R01DK080440,R01DK104656,R01ES025909,R21CA191507,and P30 DK34989(to L.Wang);VA Merit Award 1I01CX000361,NIH U01AA021840,NIH R01 DK107682,NIH R01 AA025208,US DOD W81XWH-12-1-0497(to S.Liangpunsakul),and NIH R21AA024935-01(to L.Wang and S.Liangpunsakul),and NIH R56 AI112398(to A.L.Dent). 摘　　要：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)-ɣupon 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-ɣsecretion 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. 关 键 词：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)
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