Characteristics Of Regulatory B Cells And Serum Cytokines In Patients With Chronic Hepatitis B Virus Infection During Different Immune Status

Objectives To investigate the frequencies of regulatory B cells(Bregs) in the peripheral blood and the levels of serum interleukin-10(IL-10) and interferon-γ-induced protein 10(IP-10) in different immune phases of chronic hepatitis B virus(HBV) infection.Methods Totally 63 patients with chronic HBV infection(15patients in immunue tolerant phrase, 23 patients in immune reactive phrase, 25 patients in inactive HBV carrier state) as well as 16 healthy controls were enrolled in this study. The frequencies of Bregs(CD24hi CD38 hi B cells) in the peripheral blood B cells were measured by flow cytometry. IL-10 and IP-10 levels were determined with the Human Magnetic Cytokine/Chemokine Bead Panel on the MAGPIX instrument.Results Compared to immune tolerant phase(IT) and healthy controls(HC), the frequencies of Bregs were significantly elevated in the immune reactive phase(IA)(7.11(5.82,8.18)% vs 4.40(3.48,5.50)%, P=0.010;7.11(5.82,8.18)% vs 5.32(3.11,6.05)%,P<0.001). The frequencies of mature B cells( CD24 int CD38int B cells) were significantly lower in IT group than that in HC group( 47.19(35.33,52.91)% vs57.00(48.23,61.14)%, P=0.02). Serum IL-10 and IP-10 levels were also elevated significantly in IA group as compared with IT, inactive HBV carrier state(IC) and HC group( 18.14(5.85,25.16) pg/ml vs 0.01(0.00,0.46)pg/ml, 18.14(5.85, 25.16)pg/ml vs 0.00(0.00, 0.1) pg/ml, 18.14(5.85, 25.16) pg/ml vs 0.00(0.00, 0.00) pg/ml,P all <0.001; 1720.0(1040.0, 4042.0) pg/ml vs 661.4(508.0, 940.6) pg/ml, 1720.0(1040.0,4042.0) pg/ml vs 554.7(390.1, 740.7) pg/ml, 1720.0(1040.0, 4042.0) pg/ml vs 653.2( 398.6, 715.8) pg/ml, P all <0.001). The frequencies of Bregs positively correlated with IL-10 and ALT levels(r=0.282, P=0.025; r=0.305, P=0.026) in chronic HBV infection. In addition, IL-10 and IP-10 levels were also positively correlated with ALT levels in IA group( r=0.715, P<0.001; r=0.653, P<0.001).Conclusions The frequencies of Bregs, levels of IL-10 and IP-10 were significantly different in various immune status of chronic HBV infecton. The frequencies of Bregs, IL-10 and IP-10 levels were elevated significantly in immune reactive phase(IA) of chronic HBV infection. The frequencies of Bregs positively correlated with IL-10 and ALT levels in chronic HBV infection. IL-10 and IP-10 levels were also positively correlated with ALT levels in immune reactive phase(IA) of chronic HBV infection.