Clinical Significance Of T Cell Immunoglobulin And Mucin-3 In Chronic Hepatitis C Infection

Obejective: Hepatitis C virus(HCV)infects nearly 200 million peple in the world wide,of which most are chronic infections.The mechanism of the chronicity is still unclear,but one of the most convincing point of view claims is the virus have developed capability to evade immune-mediated clearance in the chronic infected individuals.T cell exhaustion is now regarded as a significant cause of immune escape,which is associated with lots of negative regulate factors,T cell immunoglobulin and mucin-3(Tim-3),as one important parts of the negative regulate factors,has been proved its role in Chronic infectious disease,such as HBV infection and HIV infection.We aims to investigate the impact of Tim-3 in the development and prognosis of HCV infection.Methods: This study utilized 15 control subjects and 44 subjects chronically infected with HCV.The chronic hepatitis C subjects were divided into 3 groups as NoT group(patients that had not been treated),SVR group(patients achived sustained viral response after anti-viral treatment)and Rel goup(patients whose infection relapsed after anti-viral treatment).All subjects were randomly selected from the inpatients and outpatients of the Cangzhou infectious disease hospital.Serum specimens of all the subjects were collected to value the regular serum biochemical reatures including albumin,alanine transaminase,total bilirubin.13 liver tissues of the CHC patients(NoT: 3,SVR: 5,Rel: 5)were collected to examin the Tim-3expression in liver by immune-histochemical staining and quantitative real-timepolumerase chain reaction.All of the CHC patients were diagnosed according to the Guideline of prevention and treatment of hepatitis C developed by the Hepatology Branch,Infectious and Parasitology branch,Chinese Medical Assosiation.Results:1 Demographic data of all subjects were cpmparable.The albumin levels of CHC patients(NoT group 32.1±3.2 g/L,SVR group 35.2±4.2 g/L,Rel group 32.2±2.9 g/L)were significantly lower than controls(43.8±5.5 g/L),the alanine transaminase levels(NoT group 31.1±8.7 U/L,SVR group 30.1±7.9U/L,Rel group 30.2±8.2 U/L)were significantly higher than controls(11.3±6.5 U/L),P<0.05 or P<0.01.2 NoT group and Rel group had a significantly higher serum Tim-3 levels(474.3±152.5 pg/ml,473.9±144.5 pg/ml)than SVR group(176.3±108.8 pg/ml)and controls(56.0±56.9 pg/ml),P<0.05 or P<0.01.3 The serum IFN-γ level of SVR group was significantly higher than other groups.SVR patient had a obviously higher IFN-γ level(1164.0±344.5pg/ml)than NoT group(378.1±106.0 pg/ml),Rel group(375.7±132.4 pg/ml)and controls(390.8±157.9 pg/ml),the differences were all statisitcally significant,P all <0.01.4 NoT group were compared with SVR group and Rel group of Tim-3 in liver tissue.The results showed that the SVR patients had less Tim-3+ cells(10.6±1.2 /hpf)than Rel group(26.5±2.8 /hpf),p<0.01.The differences between other groups were not significant.5 SVR group with liver tissue Tim-3 mRNA level was lower than that in NoT group and Rel group.Quantitative real time PCR was performed in 3groups.Results showed that SVR group had the lowest Tim-3 mRNA level(1.0)than NoT group(2.8±0.2)and controls(2.8±0.3),the differences were statisitcally significant,P all <0.05Conclusion:1 The SVR patients had a low serun Tim-3 level than No T group and Rel group suggesting CHC patients with a serum Tim-3 levels might have a worse prognosis of anti-viral therapy.2 IFN-γ level in the SVR group was higher than NoT group and Rel group,which implied Tim-3 might have the ability to interfere synthetic section and/or secretion of IFN-γ and led to different outcomes of chronicHCV infections.