1.Relationship between HBV DNA level, expression of PD-1 on CTL and liver functions in patients with hepatitis B virus cirrhosis
Dong WANG ; Xibing GU ; Yinfang ZHU ; Yaping DAI ; Qin TANG
The Journal of Practical Medicine 2015;(7):1072-1075
Objective To explore the relationship between serum HBV DNA level , expression of PD-1 on CTL and liver functions in patients with hepatitis B virus cirrhosis. Methods 109 HBV hepatic cirrhosis patients with , HBV DNA positive , HBeAg positive and HLA-A2 positive were divided into two groups according to their HBV DNA levels,52 cases in group A, HBV DNA 2-4 log10 copies/mL, 57cases in group B, HBV DNA 5-7 log10 copies/mL , differences of HBV specific CTL surface PD-1 expressions , HBV specific CTL levels and liver functions were compared between two groups. Results HBV specific CTL surface PD-1 expressions of group A were lower than that of group B (t = 11.101, P < 0.01), HBV specific CTL levels of group A were higher than that of group B (t = 24.424, P < 0.01), ALT of group A were lower than that of group B (t = 2.652, P < 0.01), ALB of group A were higher than that of group B (t = 2.347, P < 0.05). Child-pugh rating, grade C of group A was lower than that of group B (χ2= 4.262,P < 0.05). Conclusions HBV specific CTL surface PD-1 expression levels were higher in those hepatic cirrhosis patients with , high level of serum HBV DNA, and HBV specific CTL levels were lower, liver functions damage were much serious. So, lower HBV DNA levels , lower HBV specific CTL surface PD-1 expression levels and higher HBV specific CTL levels can product relatively good effect of anti-viral treatment.
2.Study of the association between difference in cellular immunity and liver function of hepatitis B virus genotype B,C and interleukin-7 inducing follicular helper T lymphocytes
Dong WANG ; Zhonghua LU ; Qin TANG ; Zheng WANG ; Hao PEI ; Yinfang ZHU ; Decai FU ; Xibing GU
Chinese Journal of Infectious Diseases 2015;(9):522-526
Objective To investigate the association between the difference of specific cytotoxic lymphocyte (CTL) and liver function of patients with hepatitis B virus (HBV) genotype B and C infections and interleukin (IL)‐7 induced follicular helper T lymphocytes (Tfh) .Methods Sixty‐seven patients with chronic hepatitis B (CHB) hospitalized at Wuxi No .5 People′s Hospital from August 2013 to January 2015 were collected and 30 healthy blood donors were set as healthy control group .The peripheral blood IL‐7 , Tfh ,IL‐21 ,HBV specific‐CTL ,nonspecific CTL ,levels of HBV DNA ,alanine aminotransferase (ALT) and total bilirubin (TBil) were compared between patients with genotype B and C infection ,hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative CHB ,high ALT level and low ALT level .Multivariate regression analysis was performed to determine the factors associated with IL‐7 .The t test was used for quantitative data and chi‐square test was used for categorical data .Results Of the 67 CHB patients with average age of (35 .1 ± 11 .4) ,48 were male and 19 were female;32 were infected with genotype C and 35 were infected with genotype B ;40 were HBeAg‐positive CHB and 27 were HBeAg‐negative CHB ;17 were with high ALT levels and 50 were with low ALT levels .IL‐7 ,Tfh ,IL‐21 and HBV specific‐CTL levels in the peripheral blood of genotype C‐infected patients were (20 .79 ± 4 .82 ) ng/L , (3 .93 ± 0 .82)% ,(24 .77 ± 7 .52) ng/L and (0 .20 ± 0 .04)% ,respectively ,while in genotype B‐infected patients , those were (29 .13 ± 8 .17) ng/L ,(5 .92 ± 1 .92)% ,(39 .94 ± 24 .00) ng/L and (0 .40 ± 0 .06)% , respectively .Levels of IL‐7 , Tfh ,IL‐21 and HBV specific‐CTL in genotype C‐infected patients were significantly lower than those in genotype B‐infected patients (t= 5 .027 ,5 .595 ,3 .553 and 15 .133 , respectively ;all P<0 .01) .Nonspecific CTL ,HBV DNA ,ALT and TBil levels in the peripheral blood of genotype C‐infected patients were all significantly higher than those in genotype B infected‐patients (t=4 .899 ,6 .815 ,2 .763 and 4 .899 ,respectively ;all P< 0 .01) .IL‐7 ,Tfh ,IL‐21 ,HBV specific‐CTL levels in the peripheral blood of HBeAg‐positive patients were significantly lower than those in HBeAg‐negative patients (all P<0 .01) .Nonspecific CTL ,HBV DNA ,ALT and TBil levels in the peripheral blood of HBeAg‐positive patients were all significantly higher than those in HBeAg‐negative patients (all P<0 .05) .IL‐7 ,Tfh ,IL‐21 ,HBV specific‐CTL levels in the peripheral blood of patients with high ALT levels were all significantly lower than those in patients with low ALT levels (all P<0 .01) .Nonspecific CTL and HBV DNA levels in the peripheral blood of patients with high ALT levels were both significantly higher than those in patients with low ALT levels (both P<0 .01) .HBV DNA ,IL‐21 and nonspecific CTL were all correlated with IL‐7 (all P<0 .01) .Conclusion The differences of HBV specific‐CTL and liver function in CHB patients infected with genotype B and C may be correlated with interleukin‐7 induced Tfhcells.
3.Changes of programmed death receptor-1 in patients with different baseline hepatitis B virus DNA levels after treatment with adefovir dipivoxil
Yulin ZHOU ; Xuecai WANG ; Xibing GU ; Yinfang ZHU ; Xiaojuan YANG ; Juanhua WANG ; Zhong HUA
Chinese Journal of Infectious Diseases 2014;32(10):589-593
Objective To explore the changes of programmed death receptor-1 (PD-1) in chronic hepatitis B (CHB) patients with different baseline of hepatitis B virus (HBV) DNA levels after treatment with adefovir dipivoxil (ADV).Methods One hundred CHB patients with positive hepatitis B e antigen (HBeAg),1 × 104 copy/mL≤HBV DNA≤1 × 107 copy/mL,and positive human leukocyte antigen-A2 were divided into two groups according to the baseline HBV DNA level:47 cases in low virus load group whose HBV DNA level was ≤1 × 105 copy/mL; 53 cases in high virus load group whose HBV DNA level was>1 × 105 copy/mL.Both groups were treated with ADV 10 mg/d.Serum HBV DNA,HBeAg seroconversion rate,alanine aminotransferase (ALT) and total bilirubin (TBil) levels of both groups before treatment and 12 months after treatment were compared.Flow cytometry was used to test peripheral blood HBV-specific cytotoxic T lymphocyte (CTL) surface PD-1 and peripheral blood HBV-specific CTL level.Categorical data were tested by x2 test; quantitative data was compared with t-test.Results Peripheral blood HBV-specific CTL surface PD-1 of CHB patients in low virus load group was 20.17 %±1.69%,which was lower than that in high virus load group (41.38%±2.30%,t =53.02,P<0.01) ; peripheral blood HBV specific CTL levels in two groups were 0.37%±0.02% and 0.17%± 0.02%,respectively (t=50.47,P<0.01) ; ALT and TBil levels in low virus load group were both lower than those of high virus load group (t=13.07,P<0.01; t=5.06,P<0.01).Twelve months after treatment,HBV DNA of 25 cases (53.2%) in low virus load group and 10 cases (18.9%) in high virus load group were lower than the detectable level (HBV DNA<500 copy/mL,x2 =12.89,P<0.01);HBeAg seroconversion was achieved in 15 cases(31.9%) and 1 case (1.9%),respectively (x2 =16.72,P<0.01) ; peripheral blood HBV-specific CTL surface PD-1 expression levels were 9.00 % ±1.38 % and 29.40 % ± 3.76 %,respectively (t =36.80,P< 0.01) ; peripheral blood HBV-specific CTL levels were 0.65%±0.10% and0.48%±0.07%,respectively (t=9.61,P<0.01).Conclusions After treatment with ADV,along with the decrease of HBV DNA load,HBV-specific CTL surface PD-1 expression decreases,while HBV-specific CTL level increases.The changes in low virus load group are much more remarkable.
4.Relationship between PD-L1 expression and regulatory T cell infiltration in lung cancer tis-sues and their clinical significance
Yinfang SHEN ; Chuanyong MU ; Yanbin CHEN ; Lingchuan GUO ; Yehan ZHU ; Jianan HUANG
Chinese Journal of Clinical and Experimental Pathology 2015;(4):418-421,425
Purpose To investigate relationship between PD-L1 molecule expression and Treg infiltration in non-small cell lung cancer ( NSCLC) tissue and to explore their clinical significance. Methods Immunohistochemistry was used to detect the PD-L1 molecules expression and Treg infiltration of 78 NSCLC tissues. The relationship among PD-L1 expression, Treg infiltration and clinic-pathological parameters was analyzed in the patients. Results PD-L1 molecule was highly expressed in lung cancer tissues than adjacent tissues (52. 5% vs 6. 4%), and same to Foxp3 +Treg (18. 63 ± 16. 67)/HPF vs (2. 96 ± 2. 97)/HPF. There was close relationship between PD-L1 expression and Treg infiltration with lymph node metastasis and clinical stage of patients, but was no statistical correlation with patient’ s age, gender, histological type and degree of differentiation of the tumor cells. PD-L1 expression was significantly higher in advanced stage than that in early stage (70. 0% vs 41. 7%) and same to Treg infiltration (73. 3% vs 35. 4%). There were also signif-icantly higher infiltration with lymph node metastasis than that without metastasis. In addition, PD-L1 molecule expression and Foxp3 +Treg infiltration were positively correlated (rs =0. 611, F=78. 82, P=0. 023). Conclusion There was strong relationship among PD-L1 expression, Treg infiltration and disease progress in lung cancer patients, and they possibly participate in the progression and immune escape of lung cancer.
5.Relationship between genotypes HBV C and B with specific cytotoxic T lymphocyte surface PD-1 expression in patients with chronic hepatitis B
Yulin ZHOU ; Xuecai WANG ; Yongfei TAN ; Yanping ZHAO ; Weiliang DING ; Yinfang ZHU
Chinese Journal of Experimental and Clinical Virology 2014;28(4):258-261
Objective To explore relationship between genotypes HBV C and B with HBV specific cytotoxic T lymphocyte (CTL) surface programmed death receptor-1 (PD-1) and its significance in patients with chronic hepatitis B (CHB).Methods A total of 71 CHB patients were studied,human leukocyte antigen(HLA)-A2 positive,HBV DNA > 103 copies/ml,of which 34 cases(47.89%)had genotype C and 36 cases (50.70%) had genotype B.Peripheral blood HBV specific CTL surface PD-1 expression level,HBV specific CTL level,HBV DNA level,ALT and TBil levels of patients infected with genotype C and B were compared.Results HBV specific CTL surface PD-1 expression level of CHB patients infected with genotype C (37.30 ± 3.05%) was higher than that of patients infected with genotype B (26.19 ± 3.06%),t =15.47,P < 0.001,HBV specific CTL level (0.25 ± 0.03%) was lower than that of patients infected with genotype B (0.45 ±0.13%),t =21.54,P <0.001,HBV DNA level (6.75 ±0.77 log10 copies/ml) was higher than that of patients infected with genotype B (4.96 ± 1.12 log10 copies/ml),t =7.93,P < 0.001,ALT level (487.39 ± 87.36IU/L) was higher than that of patients infected with genotype B (235.25 ± 90.911U/L),t =12.32,P < 0.001,TBil level (49.73 ± 6.45) was higher than that of patients infected with genotype B (28.48 ± 5.89%),t =9.01,P < 0.001.Conclusion Peripheral blood HBV specific CTL surface PD-1 expression level of CHB patients infected with genotype C was higher than that of patients infected with genotype B,resulting in lower HBV specific CTL level and higher HBV DNA level of patients infected with genotype C than patients infected with genotype B,so damage to liver functions was more serious than patients infected with genotype B.
6.Relationship between viral genotypes and follicular helper T lymphocyte and interleukin-21 and its significancein patients with HBV-induced hepatic cirrhosis
Xibing GU ; Yinfang ZHU ; Juanhua WANG ; Zhong HUA ; Zhonghua LU ; Xiaojuan YANG ; Yueqin XU
Chinese Journal of Experimental and Clinical Virology 2014;28(5):327-329
Objective To explore relationship between different HBV genotypes and peripheral blood follicular helper T lymphocyte (Tfh) and interleukin-21 (IL-21) and its significance in patients with HBV-induced hepatic cirrhosis.Methods HBV genotypes were tested in 59 cases of cirrhotic hepatitis B with positive human leukocyte antigen (HLA)-A2,differences of Tfh and IL-21 between patients infected with genotype B and genotype C were compared and its significance was investigated.Results In 59 cases of cirrhotic hepatitis B,36 cases (61.02%) were infected with genotype C,22 cases (37.29%) were infected with genotype B and 1 case (1.69%) was infected with genotype B and C.Peripheral blood Tfh level of genotype C was(2.89% ± 1.44%),lower than that of genotype B (4.65% ± 1.37%),t =3.01,P <0.01,IL-21 level of genotype C was (14.62 ± 2.12 ng/L),lower than that of genotype B (32.27 ± 11.25ng/L),t =4.12,P <0.01,HBV specific cytotoxic T lymphocyte(CTL)level of genotype C was (0.17% ±0.02%),lower than that of genotype B(0.37% ±0.03%),t =3.12,P <0.01,HBV DNA level of genotype C was (6.95 ± 0.75log10copies/ml),higher than that of genotype B (5.02 ± 0.36 log10 copies/ml),t =3.03,P < 0.01.Conclusion Compared with cirrhotic hepatitis B patients infected with genotype B,peripheral blood Tfh level of patients infected with genotype C was lower,causing lower IL-21 level and lower HBV specific CTL level,which result in higher HBV DNA level.
7.Prevalence of infections with soil-borne intestinal nematodes amongst kindergarten children in Hangzhou
Huan YE ; Li-Hui ZHANG ; Ren ZHANG ; Jun YANG ; Hang-Lin MA ; Li-Na TONG ; Qing-Long FENG ; Qing-Hua DU ; Xiao-Jun YE ; Yingyan CAI ; Yinfang ZHU ; Qilong ZHANG ; Zhenxing YANG ;
Chinese Journal of General Practitioners 2003;0(06):-
Objective To study the prevalence of common infections with soil-borne intestinal nematodes amongst kindergarten children aged 3 to 6 years in Hangzhou,Zhejiang Province to provide evidence for determination of the priority of disease prevention and control.Methods Totally,1667 preschool children were selected from 14 kindergartens of Classes A,B and C in east,middle and west Hangzhou.Perianal skin Scotch Tape(a short strip of sealing cellophane pressure-sensitive tape)specimens were collected for detection of eggs of Enterobius vermicularis,and stool specimens for eggs of Ascaris lumbricoides,Ancylostoma duodenale and Trichuris trichiura by Kato-Katz method and saturated brine floatation,as well as questionnaire interview,for all the children.Results Two hundred and sixteen of 1667 children examined were found infected with common soil-borne intestinal nematodes,with an overall prevalence of 12.96%,4.44% for Enterobius vermicularis,8.28% for Ascaris lumbricoides,0.54% for Trichuris trichiura and 0.24% for Ancylostoma duodenale.Prevalence of infection of common intestinal nematodes was 7.31% in children of the Class A kindergartens,12.60% of Class B,and 21.47% of Class C,with statistically significant difference(?~2 = 49.95,P