Impaired Antibody Synthesis in Patients With Chronic Hepatitis B Infection

Abstract

In vitro synthesis of the anti-HBc, anti-HBs and polyclonal IgG and IgM classes of antibodies were determined from supernatants of peripheral blood mono-nuclear cells cultured in the presence of pokeweed mitogen. Thirty-seven patients with chronic hepatitis B and 10 healthy control subjects whose sera were positive for anti-HBs formed the study group. Twenty-four of 37 patients showed histologic evidence of chronic active hepatitis B while the remaining 13 patients had chronic persistent hepatitis B. Lymphocytes from chronic persistent hepatitis B, chronic active hepatitis B and healthy controls secreted similar levels of IgM. However, IgG synthesis was markedly impaired (p less than 0.002) in the chronic persistent hepatitis B group as compared with healthy controls or chronic active hepatitis B patients. In vitro anti-HBc production and serum anti-HBc titers correlated directly with hepatocellular inflammation and inversely with serum hepatitis B virus DNA. Anti-HBc synthesis was significantly higher in chronic active hepatitis B patients who exhibited a more pronounced hepatocellular damage when compared to chronic persistent hepatitis B patients who had little or no liver cell injury.

Adeno-Associated Virus Vector Mediated Delivery of the HBV Genome Induces Chronic Hepatitis B Virus Infection and Liver Fibrosis in Mice

“…There was no direct cytopathic effects on hepatocytes by HBV infection by the presence of a lot of asymptomatic chronic HBV carriers with no signs of liver injury[42]. Previous studies found defects of the immune response in HBV chronic infected patients, including reduction of HBV-specific antibodies[43, 44], delayed lymphocytes migration, and increment of suppressor lymphocytes[45]. Circulating HBsAg is probably the mechanism of defective immune response in HBV carriers[43, 46].…”

Cellular immune responses to hepatitis B virus antigens in man

“…Thus, patients with CPH exhibited significantly higher HBV-DNA levels in sera compared with patients with CAH. IgG synthesis after PWM stimulation was markedly impaired in the CPH group as compared with CAH patients and "healthy" controls ( 187). Similarly, significantly decreased responsiveness of the same lymphocyte population to PWM.…”

“…In most studies in vitro where the capacity of PBL or purified B-cells from patients with chronic liver disease type B to produce anti-HBs after stimulation with PWM (172, [185][186][187] or HBsAg (154,171,186) has been evaluated, anti-HBs has been absent from all carrier lymphocyte supernatants. Polyclonal IgG and IgM, as well as detectable amounts of anti-HBc were, however, produced in most carriers after PWM stimulation (1 72, 185-1 87).…”

Upregulation of MHC class II antigen on dendritic cells from hepatitis B virus transgenic mice by interferon‐γ: abrogation of immune response defect to a T‐cell‐dependent antigen

“…2 It has been reported that both cellular and humoral immune responses to HBV-related antigens are defective in human HBV carriers [3][4][5][6] and in HBV-transgenic mice. 7 HBV carriers can not produce specific antibody to hepatitis B surface antigen (HBsAg) in vivo and most of these studies in vitro have documented the abnormalities in function of regulatory and helper T cells, and the inability of B cells to produce specific antibody in response to HBsAg.…”

“…7 HBV carriers can not produce specific antibody to hepatitis B surface antigen (HBsAg) in vivo and most of these studies in vitro have documented the abnormalities in function of regulatory and helper T cells, and the inability of B cells to produce specific antibody in response to HBsAg. [2][3][4][5][6] On the other hand, some investigators could not detect any substantial defects in the function of T and B lymphocytes in HBV carriers. 8,9 Under such diverse reports about the immune response of HBV carriers on HBV-regulated antigens, it was interesting to elucidate the immune response of HBV carriers to HBV-unrelated antigens to have further insight into the exact immune status of HBV carriers.…”