| Objective: HBV-related acute-on-chronic liver failure(ACHBLF)has become an important factor affecting the quality of life of chronic hepatitis b(CHB)patients due to rapid disease progression and high mortality.At present,the pathogenesis of ACHBLF and the influencing factors in the process from chronic hepatitis B to pre-ACHBLF to ACHBLF are still unknown.Changes in immune cells and mediated liver injury are important factors affecting the prognosis of ACHBLF patients.However,the role of many newly discovered immune cells in ACHBLF remains to be studied.The aim of this study is to analyze the expression and significance of T cell subtypes and MDSCs in pre-ACHBLF and ACHBLF patients and explore the role of T cells and MDSCs in the development of ACHBLF.Methods: A total of 27 patients with ACHBLF and 15 patients with pre-ACHBLF was enrolled from August 2017 to May 2019 in Shijiazhuang Fifth Hospital.Twenty-two CHB patients and 26 healthy subjects were selected as the control group.Clinical data,liver function,blood routine indexes were collected.The percentages of peripheral helper T cells(Th)1,Th9,Th17,regulatory T cells(Tregs),Cytotoxic T cells(Tc)1,Tc 9,Tc 17 as well as myeloid-derived suppressor cells(MDSCs)and its subtypes were determined by flow cytometry.The correlation between the percentages of immune cells and liver function index or inflammatory indicators was analyzed.Statistical analysis was performed on the results using SPSS 21.0.Results: 1.Peripheral Th1 cells in pre-ACHBLF group(11.11%,P=0.032)and ACHBLF group(9.02%,P=0.002)were lower than those in HC group(18.58%).Th9 cells in pre-ACHBLF group(0.77%)were also lower than those in HC group(2.33%,P=0.040).However,Th17 cells in pre-ACHBLF group(6.40%)were higher than those in HC group(3.00%,P=0.025)and CHB group(1.63%,P=0.002).Th17 cells in ACHBLF group(4.03%)were higher than those in CHB group(P=0.007).2.Th9 cells were negatively correlated with ALT(r=-0.638,P=0.042),TP(r=-0.733,P=0.025),GLB(r=-0.817,P=0.007),IBIL(r=-0.17,P=0.030),and APTT(r=-0.700,P=0.036),but positively correlated with ALB/GLB(r=0.748,P=0.020)in pre-ACHBLF patients.Furthermore,Th17 cells were negatively correlated with IBIL(r=-0.750,P=0.020).However,there was no correlation between Th cells and liver function indexes in ACHBLF patients.3.Th9 cells were negatively correlated with lymphocytes(r=-0.828,P=0.006)and positively correlated with PLR(r=0.783,P=0.013)in pre-ACHBLF patients.Th1 cells were positively correlated with platelets(r=0.761,P=0.003),but negatively correlated with RPR(r=-0.753,P=0.003)and MPR(r=-0.611,P=0.046)in ACHBLF patients.4.Tc9 cells in pre-ACHBLF group(0.86%)were significantly lower than those in HC group(4.46%,P<0.001).Tc17 cells in pre-ACHBLF group(5.23%)and ACHBLF group(5.37%)were higher than those in CHB group(0.89%,P<0.001)and HC group(2.24%,P<0.05).There was no significant difference in Tc1 cell frequency among the four groups(28.90% vs 18.27% vs 20.91% vs 20.64%,F=1.048,P=0.381).5.Tc9 cells were negatively correlated with ALT(r=-0.783,P=0.013),AST(r=-0.717,P=0.030),GLB(r=-0.683,P=0.042),IBIL(r=-0.683,P=0.042),and APTT(r=-0.750,P=0.020)in pre-ACHBLF patients.Tc17 cells were negatively correlated with TBIL(r=-0.750,P=0.020).There was no correlation between Tc cells and liver function indexes in ACHBLF patients.6.Tc9 cells were positively correlated with platelets(r=0.667,P=0.050)and PLR(r=0.833,P=0.005),but negatively correlated with lymphocytes(r=-0.828,P=0.006)in pre-ACHBLF patients.There was also a negative correlation between Tc17 cells and lymphocytes(r=-0.795,P=0.010).Tc1 cells were positively correlated with platelets(r=0.626,P=0.022)and negatively correlated with RPR(r=-0.599,P=0.031)in ACHBLF patients.7.The frequencies of Tregs in the pre-ACHBLF(1.74%)and the ACHBLF group(1.91%)were higher than those in CHB group(0.60%,P<0.05)and HC group(0.55%,P<0.05).There was no significant difference in Th17/Tregs ratio among the four groups(4.80 vs 2.99 vs 3.48 vs 2.11,2 =3.817,P=0.282).8.The ratio of Th17/Tregs was negatively correlated with AST(r=-0.746,P=0.033)and APTT(r=-0.938,P=0.001)in pre-ACHBLF patients.The frequencies of Tregs were positively correlated with AST(r=0.741,P=0.006),IBIL(r=0.587,P=0.045),PT(r=0.605,P=0.037),TT(r=0.621,P=0.031),and PTA(r=-0.642,P=0.025)in ACHBLF patients.Th17/Tregs was negatively correlated with AST(r=-0.773,P=0.005),TBIL(r=-0.809,P=0.003),DBIL(r=-0.700,P=0.016),IBIL(r=-0.827,P=0.002),PT(r=-0.773,P=0.005),TT(r=-0.868,P=0.001),INR(r=-0.755,P=0.007),and APTT(r=-0.791,P=0.004),but positively correlated with PTA(r=0.827,P=0.002).9.MDSCs in pre-ACHBLF and ACHBLF group(5.10%)were higher than those in CHB group(1.24%,P<0.001)and HC group(1.04%,P<0.001).Furthermore,PMN-MDSCs in pre-ACHBLF group(0.19%),ACHBLF group(0.23%)and CHB group(0.11%)was higher than HC group(0.05%,P<0.001).There was no significant difference in M-MDSCs among the four groups(0.40% vs 0.26% vs 0.97% vs 0.64%,2=4.514,P=0.211).10.MDSCs were positively correlated with ALT(r=0.643,P=0.010),AST(r=0.664,P=0.007),TBIL(r=0.614,P=0.015),DBIL(r=0.807,P=0.000),IBIL(r=0.793,P=0.007),and APTT(r= 0.793,P=0.007),but negatively correlated with PTA(r=-0.639,P=0.010)in pre-ACHBLF patients.Moreover,MDSCs were also positively correlated with neutrophil number(r=0.727,P=0.002),mononuclear cell number(r=0.767,P=0.001),NLR(r=0.571,P=0.026),MLR(r=0.786,P=0.001,SIRS(r=0.846,P<0.001)in pre-ACHBLF patients.However,MDSCs were positively correlated with TBIL(r=0.545,P=0.003)and DBIL(r=0.530,P=0.004),and negatively correlated with lymphocytes(r=-0.435,P=0.023)in ACHBLF patients.Conclusions:1.Peripheral Th1,Th9 and Tc9 cells were decreased,and Th17 and Tc17 cells were increased in pre-ACHBLF and ACHBLF patients.The change was associated with clinical parameters.The results indicated that effctor T cells had important effects on the development of ACHBLF.2.The increase of Tregs and MDSCs was found in the pre-ACHBLF and ACHBLF group.The change of those two suppressive cells was also associated with clinical paremeters.The results suggested that Tregs and MDSCs may be important factors affecting the disease progression in ACHBLF.3.The interaction among various immune cells affects the development of ACHBLF.Our study contributes to understanding the unifying immunological mechanism of ACHBLF pathogenesis. |
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