Human Serum Albumin and the Enigma of Chronic Hepatitis Type B

Hellström, U.; Sylvan, Staffan

doi:10.1111/j.1365-3083.1986.tb01983.x

Cited by 14 publications

(3 citation statements)

References 41 publications

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“…The circulatory pool of B cells from the majority (11,13) of chronic carriers of HBsAg contained B cells sensitized lo HSA with the capacity to seerete IgG antibodies with specificity for albumin, when stimulated with low coneentrations of E. (Y>//-derived core proiein in the presence of autologous T cells in vitro. IgG anti-HSA-containing eulture supernatanls also contained IgG antibodies wilh specificity for E. r«/f-derived core protein, indicating that the host immune system in these individuals has been challenged with Cgene-derivcd structures in association with HSA.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the Immune Response to Hepatitis B Virus and Human Serum Albumin. III. Induction of Anti‐Albumin Antibody Secretion In Vitro by C‐Gene‐Derived Proteins in Peripheral B Cells from Chronic Carriers of HBsAg

Hellström

Sylvan

1992

Scand J Immunol

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The circulatory pool of B cells from the majority (11/13) of chronic hepatitis B surface antigen (HBsAg) carriers contained sensitized B cells with the capacity to secrete IgG antibodies with specificity for human serum albumin (HSA), when stimulated with E. coli-derived core protein at low concentrations in vitro. The IgG anti-HSA secretion was dependent upon and regulated by T cells, and optimal secretion was obtained at T/B-cell ratios of 1.0-4.0, varying for different individuals. The level of anti-HSA secretion was higher for patients with on-going viral replication as assessed by hepatitis B virus (HBV)-DNA in serum. Culture supernatants containing anti-HSA antibodies also contained anti-HBc antibodies, as detected by enzyme-linked immunosorbent assay (ELISA) where the solid phase was charged with E. coli-derived core protein, or the synthetic peptides corresponding to the 75-84 and 132-147 sequences in the C region of HBV. In contrast, IgG anti-HBc (E. coli-derived), but no anti-HSA or anti-HBc 75-84, 132-147 antibodies, were detected at similar T/B-cell ratios in cell cultures from 5/6 individuals with naturally acquired immunity to hepatitis B. These data indicate that peripheral B cells from the majority of HB-immune donors are sensitized to unique (e.g. non-albumin associated) structures in the nucleocapsid of HBV, while B cells in the majority of chronic HBsAg carriers are sensitized to linear C-gene-derived structures in association with the host 'self'-component HSA.

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Section: Discussionmentioning

confidence: 99%

Regulation of the Immune Response to Hepatitis B Virus and Human Serum Albumin. III. Induction of Anti‐Albumin Antibody Secretion In Vitro by C‐Gene‐Derived Proteins in Peripheral B Cells from Chronic Carriers of HBsAg

Hellström

Sylvan

1992

Scand J Immunol

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“…We have earlier hypothesized that the break in tolerance lo 'self (HSA) could permit the production of anti-HSA antibodies of an autoimmune nature. Such antibodies eould participate in antibody-dependent lytic reactions, resulting in destruction of albumin-producing non-infected hepatocyles during HBV infection [6]. The autoimmune anti-HSA reactivity and its regulation during chronic infection with HBV therefore needs further elucidation.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the Immune Response to Hepatitis B Virus and Human Serum Albumin

Hellström

Sylvan

1989

Scand J Immunol

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Peripheral B and T cells sensitized to human serum albumin (HSA) were found in a cohort of patients chronically infected with hepatitis B virus (HBV). Throughout this study, two groups of symptomatic chronic hepatitis B surface antigen (HBsAg) carriers could be distinguished, characterized by divergent T-cell regulation of the spontaneous IgG anti-HSA secretion. Patients in a quiescent phase of the disease [patients with chronic persistent hepatitis B (CPH), anti-HBe reactivity and absence of viral replication, group A] had circulatory in vivo HBsAg-HSA preactivated B cells with the capacity to secrete spontaneously IgG antibodies with specificity for HSA when isolated and cultured. The addition of autologous T lymphocytes at a T/B-cell ratio of 8.0 suppressed the spontaneous anti-HSA secretion. In contrast, patients in an active stage of the disease exhibited in vivo preactivated T cells exerting helper cell functions on the spontaneous IgG anti-HSA secretion. Memory T cells, sensitized to low concentrations of HBsAg-HSA with disparate regulatory functions, were also detectable in the two groups of patients.

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“…Addition of the pre-S subunits to HBsAg appears to be necessary in formation of the external coat of the Dane particle, the complete virus, and the filamen tous form of HBsAg. The 22-nm spherical form of HBsAg, common in nonreplicative HBsAg carriers and in the hepatitis vaccine, is relatively free of pre-S subunits [14], It is thought that pre-S| is necessary for virus assembly and pre-S2 corresponds to the poly merized human serum albumin receptor, which may be important in virus binding to hepatocytes [15][16][17].…”

Section: Hepatitis B Virusmentioning

confidence: 99%