The Expression And Clinical Significance Of Costimulate Molecules On CTL, And IFN-γ In The Patients With HBV-associated Acute-on-chronic Liver Failure

The first section: The expression of costimulate molecules on peripheral T cells in patients with acute-on-chronic liver failure and the relationship with prognosisBackground: Acute-on-chronic liver failure which mostly caused by HBV in China has a high case fatality and a complicate pathogenesy。Hadro- immune response caused by HBV was generally accepted as an important factor for ACLF.Costimulatory molecules signal can regulate the activation of lymphocyte. Internal study has found that programmed death1(PD-1)was high expressed on specificity CTL,but the immune state dynamic changed during ACLF,and there's little research about the expression of PD-1, Cytotoxic T lymphocyte-associated antigen 4(CTLA-4) and CD28 on the lymphocyte of HBV- associated acute-on-chronic liver failure(HBV-ACLF)during different periods .Objective: To Investigate the espression , dynamic change and clinical significance of PD-1/PD-L1,CTLA-4 and CD28B on CTL of HBV-ACLF patients during different periods.Methods: Detected the expression of PD-1/PD-L1,CTLA-4 and CD28 on periph CTL cells in 43 HBV-ACLF patient ,15 CHB patients and 15 health adults by fluorescence-activated cell sorter; observed dynamic changes of costimulatory molecules during the nonage, metaphase and advanced stage of ACLF;compared the differences of negativity costimulatory molecules expression on CTL cells between survival group and unsurvival group .Results: 1.The expression of costimulate molecular on periph CTL cells in 43 HBV-ACLF patient ,15 CHB patients and 15 health adults are as follows:①CTL:(22.62±9.61)%,(13.68±3.99)%,(17.45±4.02)%;②CD28:(25.37±11.25)%,(10.07±4. 32)%,(18.10±3.70)%;③PD-1: (14.93±7.03)%,(9.95±1.93)%,(6.41±1.93)%;④C TLA-4: (15.06±4.87)%, (11.06±2.60)%, (6.25±2.42)% .There are significant difference among the three groups .2.The expression of costimulate molecular on peripherl CTL cells in the nonage, metaphase and advanced stage of 43 ACLF patients are as follows:①CTL: (31.59±6.50)%, (20.88±5.92)%, (13.21±6.58)%;②CD28: (35.94±9.09)%, (24.75±6.90)%, (13.07±3.90)%;③P D-1:(6.19±3.02)%,(13.53±3.98)%,(23.22±3.93)%;④P D-L1:(3.70±2.17)%,(7.10±2.69)%,(12.31±3.82)%;⑤C TLA-4:(8.79±2.10)%,(12.41±2.42)%,(18.21±2.23)%.There are also significant differences among the three periods.3.The differences of the expression of CTLA -4 ,PD-1and PD-L1 on CTLcells of ACLF patients between the survival group and the unsurvival group are significant , with a result as follows:①CTLA-4:(10.12±4.71)%,(14.21±4.86)%(P= 0.004);②PD-1:(11.05±6.87)%, (18.31±5.80 )% (P=0.006)Conclusion: The expression of costimulatory molecules can partly reflect patient's immune level;the advance of CD28 may signify the enhancement of immune; the heighten of CTLA-4,PD-1 and PD-L1 may predict immune suppression; CTLA-4,PD-1 and PD-L1of the survival group were lower than unsurvival group,which means that the higher expression of negativity costimulatory molecules was detrimental to the prognosis of ACLF.Costimulatory molecules may have a certain value for evaluating immune state ,guiding the regulation of immunity.The second section: The expression of peripheral blood serum IFN-γin patients with acute-on-chronic liver failure and the relationship with positive costimulatory molecules CD28Background: Cytoimmunity ,which induces hepatic lesion by cytolytic t lymphocyte , is more important than humoral immunity for the mechanism of ACLF.Positive costimulatory molecules participating in lymphocyte activation is a key signaling molecule for cytoimmunity. IFN-γwas secreted by activatory Th1,which played an important role in virus cleaning and hepatocyte damage,the relationship between IFN-γand CD28 have not been found. Objective:To Investigate the change and clinical significance of IFN-γof ACLF patients during different period.Methods: Detected IFN-γfrom peripheral blood serum of 43 HBV-ACLF patient ,15 CHB patient and 15 health adult by ELISA, observed dynamic changes of IFN-γduring the nonage, metaphase and advanced stage of ACLF, analyze the associativity of IFN-γand CD28.Results: T The level of peripheral blood serum IFN-γof the ACLF, CHB and normal control are (405.2±73.4)pg/ml,(311.2±36.5)pg/ml and(356.4±36.7)pg/ml respectively,which has significant differences. There are also significant differences between the three periods.The level of peripheral blood serum IFN-γduring the nonage ,metaphase and advanced stage are (474.4±85.6)pg/ml (,391.7±34.4)pg/ml and(296.5±56.1)pg/ml separately. there is positive correlation between IFN-γand CD28 expressed on CTL cells of ACLF patients with a correlation coefficient r=0.72457, which has a statistical significance.Conclusion: The level of peripheral blood serum IFN-γadvanced notablely in ACLF patients,and has a positive correlation with CD28. IFN-γmay have a certain value for evaluating immune state ,guiding clinical therapy and predicting prognosis.