Expression and role of interleukin 35-producing B cells and interleukin 35 from peripheral blood of patients with chronic hepatitis B / 中华传染病杂志

ABSTRACT

Objective To explore the level of interleukin 35-producing B cells (i35-Breg) as well as its effect factors,interleukin-35 (IL-35),in peripheral blood of patients with chronic hepatitis B (CHB),and their relationship with hepatitis B virus (HBV) DNA and liver inflammatory degree.Methods A total of 35 treatment-naive CHB patients,17 interferon (IFN)-treated HBeAg-positive CHB patients and 15 healthy controls (HC) were enrolled.The levels of i35-Breg and IL-35 in peripheral blood were tested by flow cytometry and enzyme-linked immunosorption assay (ELISA).Kruskal-Wallis test,Wilcox rank sum test and two variables correlation analysis were used for statistical analysis.Results The percentage of i35-Breg cells as well as IL-35 level in peripheral blood of naive CHB patients were 3.05％ (0.89％,4.97％) and 2.81 μg/L (0.30 μg/L,12.33 μg/L),respectively,which were both significantly higher than those in HC group,which were 0.17％ (0.13％,0.45％) and 0.17 μg/L(0,1.93 μg/L),respectively.The difference were statistical significant (Z=-3.309 and-2.419,respectively,P=0.001 and 0.016,respectively).The peripheral level of i35-Breg was negatively correlated with the viral load in treatment-naive CHB patients (r=-0.529,P=0.008),while there was no correlation between the peripheral level of IL-35 and the viral load in treatment-naive CHB patients (r=0.11,P=0.54).The levels of i35-Breg and IL-35 in HBeAg positive CHB patients were 3.16％ (1.34％,5.62％) and 4.58μg/L (0.79μg/L,22.37 μg/L),respectively,which were both higher than those in HC group.The difference was statistically significant (F=3.39 and 3.37,respectively,both P＜0.01).Compared to HC group,the IL-35 levels in peripheral blood of CHB patients with ALT and AST levels less than 300 U/L were 3.03 μg/L (0.74 μg/L,22.37 μg/L) and 3.25 μg/L (0.83 μg/L,22.35 μg/L),respectively,with statistically significant difference (F=2.868 and 3.114,respectively,both P＜0.01).Compared to HC group,the peripheral level of i35-Breg in treatment-naive CHB patients with ALT levels less than 300 U/L was 3.14％ (1.03％,4.65％),with statistically significant difference (F=3.219,P=0.004).The IL-35 level showed a decreased trend in CHB who received IFN therapy,but there was no statistically significant difference (x2 =1.45,P =0.48).Furthermore,the baseline IL-35 level in patients who developed sustained viral response (SVR) was 0 (0,13.33 g/L),which was lower than that in patients who developed partial or primary no response 0.61 μg/L (0,24.72 μg/L).However,there was no statistical difference (F=0.75,P =0.68).Conclusions i35-Breg as well as its effect factor,IL-35,are involved in the progression of chronic HBV infection.The percentage of i35-Breg cells as well as IL-35 level in peripheral blood of treatment-naive CHB patients are increased.The peripheral level of i35-Breg is negatively correlated with the viral load,while there is no correlation between the peripheral level of IL-35 and the viral load.The percentage of i35-Breg cells as well as IL-35 level in CHB patients with low inflammatory degree are increased.