Expression Of Ascl2 In Chronic Hepatitis C And Its Relationship With Serum Globulin

Hepatitis C is an infectious disease caused by the hepatitis C virus(HCV)that accompanies severe or mild liver inflammation.The initial entrance of HCV virions into host cells may activate immune response and lead to acute symptoms including liver injury.A small number of cases(15%)will spontaneously resolve the infection,while the vast majority of those exposed to the virus may develop into a chronic HCV infection state and followed with a persistent immune response.In addition to liver inflammation,some patients can be combined with extrahepatic manifestations caused by immune dysfunction,including serum globulin increase.However,the observation in clinical showed that the increase of serum globulin was not associated with the severity of liver inflammation,and the effective antiviral therapy could decrease the level of serum globulin,which may be related to the immune disorder caused by HCV.The increase of serum globulin is related to the abnormal proliferation and differentiation of B lymphocytes.Follicular helper T(Tfh)cells,a recently identified subset of CD4+T cells,which are specialized providers of T cell help to B cells,and are essential for germinal center formation,affinity maturation,and the development of most high affinity antibodies and memory B cells.When infected with HCV,the individures may suffer from differentiation imbalance of Tfh cell,which is a multistage,multifactorial process involving the control of transcription factors.Bcl-6 is currently considered as the main transcription factor involved in Tfh cell development,but a recent study suggests that achaete-scute homologue 2(Ascl2)may initiate Tfh cell development before Bcl-6,and even more important than Bcl-6.This study was mainly to investigate the expression of Ascl2 m RNA in Tfh cells and its relationship with serum globulin in patients with CHCObjective1.To investigate the expression of CD4+T cell subsets in PBMC of chronic hepatitis C patients and healthy volunteers;2.To determine the relationship between Tfh cells and serum globulin in chronic HCV patients;3.To investigate the expression of Tfh transcription factor Ascl2,which may have a important role in the process of chronic HCV infection.Methods Forty-six CHC patients and thirty-two healthy control were enrolled,and the proportion of Tfh cells and its subset group(CD4+CXCR5+PD-1+T cells)in PBMC were detected by flow cytometry.Serum globulin level was detected by automatic biochemical analyzer,expressions of Ascl2 m RNA in Tfh cell was determined by real-time PCR.Result In CHC patients' peripheral blood,the frequency of Tfh cell is positive correlation with B cell(r=0.5823,p=0.0112),the frequency of B cell is positive correlation with serum globulin(r=0.4509,p=0.0316),the frequency of Tfh cells is positive correlation with serum globulin(r=0.5835,p=0.0383);the expression of Ascl2 m RNA significantly increased in Tfh cells of chronic hepatitis C patients' PBMC(t=4.5522,P=0.0019),the expression of Ascl2 m RNA is positive correlation with serum globulin(r=0.5788,P=0.3010).