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Virus-specific immune response in HBeAg-negative chronic hepatitis B: relationship with clinical profile and HBsAg serum levels.

Loggi E, Bihl FK, Cursaro C, Granieri C, Galli S, Brodosi L, Furlini G, Bernardi M, Brander C, Andreone P - PLoS ONE (2013)

Bottom Line: The total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups.The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients.Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Surgical Scinces, University of Bologna, Bologna, Italy.

ABSTRACT

Background aims: The immune impairment characterizing chronic hepatitis B (cHBV) infection is thought to be the consequence of persistent exposure to viral antigens. However, the immune correlates of different clinical stages of cHBV and their relation with different levels of HBsAg have not been investigated. The aim of the present study was to evaluate the relationship between HBV-specific T cells response and the degree of in vivo HBV control and HBsAg serum levels in HBeAg-HBeAb+ cHBV.

Methods: Peripheral blood mononuclear cells from 42 patients with different clinical profiles (treatment-suppressed, inactive carriers and active hepatitis) of cHBV, 6 patients with resolved HBV infection and 10 HBV-uninfected individuals were tested with overlapping peptides spanning the entire HBV proteome. The frequency and magnitude of HBV-specific T cell responses was assessed by IFNγ ELISPOT assay. Serum HBsAg was quantified with a chemiluminescent immunoassay.

Results: The total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups. However, inactive carriers targeted preferentially the core region. In untreated patients, the breadth of the anti-core specific T cell response was inversely correlated with serum HBsAg concentrations as well as HBV-DNA and ALT levels and was significantly different in patients with HBsAg levels either above or below 1000 IU/mL. The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients.

Conclusions: Different clinical outcomes of cHBV infection are associated with the magnitude, breadth and specificity of the HBV-specific T cell response. Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control.

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Related in: MedlinePlus

Breadth and magnitude of anti-HBV specific T cell response in the four groups of patients.A) Breadth (number of targeted peptides) and B) magnitude (number specific cells) of the anti-HBV specific T cell response in the four patients groups. Total magnitude was determined by adding magnitudes obtained for all targeted peptides by each patient. Each symbol represents an individual patient, with black horizontal bars showing the median values per patient group.
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pone-0065327-g001: Breadth and magnitude of anti-HBV specific T cell response in the four groups of patients.A) Breadth (number of targeted peptides) and B) magnitude (number specific cells) of the anti-HBV specific T cell response in the four patients groups. Total magnitude was determined by adding magnitudes obtained for all targeted peptides by each patient. Each symbol represents an individual patient, with black horizontal bars showing the median values per patient group.

Mentions: To assess if a specific immune profile can be associated to a clinical category of HBV infection, virus-specific T-cell responses in 42 anti-HBe-positive chronic HBsAg carriers with different virological profiles and in 6 patients with resolved HBV infection were tested by using ELISpot assay after in vitro T cell expansion with synthetic, overlapping peptides. A group of 10 HBV negative subjects was included as controls and did not show any reactivity to the peptides library (data not shown). Among chronically HBV infected individuals, the majority of patients showed a HBV-specific immune response, with the percentage of patients with at least one targeted sequence being marginally higher among IC (92%) compared to that of the TC and the CHB (81% and 77%, respectively, p>0.05). IFN-gamma producing T cells were detected in all but one anti-HBc-positive subjects. No significant differences in the breadth (i.e. the number of targeted peptides) nor in the total magnitude (i.e. additive magnitude of all peptide specific responses in an individual) of immune response were observed between the four groups (Figure 1), indicating that quantitative aspects of the responses do not explain the different clinical outcome between the four groups.


Virus-specific immune response in HBeAg-negative chronic hepatitis B: relationship with clinical profile and HBsAg serum levels.

Loggi E, Bihl FK, Cursaro C, Granieri C, Galli S, Brodosi L, Furlini G, Bernardi M, Brander C, Andreone P - PLoS ONE (2013)

Breadth and magnitude of anti-HBV specific T cell response in the four groups of patients.A) Breadth (number of targeted peptides) and B) magnitude (number specific cells) of the anti-HBV specific T cell response in the four patients groups. Total magnitude was determined by adding magnitudes obtained for all targeted peptides by each patient. Each symbol represents an individual patient, with black horizontal bars showing the median values per patient group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672146&req=5

pone-0065327-g001: Breadth and magnitude of anti-HBV specific T cell response in the four groups of patients.A) Breadth (number of targeted peptides) and B) magnitude (number specific cells) of the anti-HBV specific T cell response in the four patients groups. Total magnitude was determined by adding magnitudes obtained for all targeted peptides by each patient. Each symbol represents an individual patient, with black horizontal bars showing the median values per patient group.
Mentions: To assess if a specific immune profile can be associated to a clinical category of HBV infection, virus-specific T-cell responses in 42 anti-HBe-positive chronic HBsAg carriers with different virological profiles and in 6 patients with resolved HBV infection were tested by using ELISpot assay after in vitro T cell expansion with synthetic, overlapping peptides. A group of 10 HBV negative subjects was included as controls and did not show any reactivity to the peptides library (data not shown). Among chronically HBV infected individuals, the majority of patients showed a HBV-specific immune response, with the percentage of patients with at least one targeted sequence being marginally higher among IC (92%) compared to that of the TC and the CHB (81% and 77%, respectively, p>0.05). IFN-gamma producing T cells were detected in all but one anti-HBc-positive subjects. No significant differences in the breadth (i.e. the number of targeted peptides) nor in the total magnitude (i.e. additive magnitude of all peptide specific responses in an individual) of immune response were observed between the four groups (Figure 1), indicating that quantitative aspects of the responses do not explain the different clinical outcome between the four groups.

Bottom Line: The total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups.The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients.Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Surgical Scinces, University of Bologna, Bologna, Italy.

ABSTRACT

Background aims: The immune impairment characterizing chronic hepatitis B (cHBV) infection is thought to be the consequence of persistent exposure to viral antigens. However, the immune correlates of different clinical stages of cHBV and their relation with different levels of HBsAg have not been investigated. The aim of the present study was to evaluate the relationship between HBV-specific T cells response and the degree of in vivo HBV control and HBsAg serum levels in HBeAg-HBeAb+ cHBV.

Methods: Peripheral blood mononuclear cells from 42 patients with different clinical profiles (treatment-suppressed, inactive carriers and active hepatitis) of cHBV, 6 patients with resolved HBV infection and 10 HBV-uninfected individuals were tested with overlapping peptides spanning the entire HBV proteome. The frequency and magnitude of HBV-specific T cell responses was assessed by IFNγ ELISPOT assay. Serum HBsAg was quantified with a chemiluminescent immunoassay.

Results: The total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups. However, inactive carriers targeted preferentially the core region. In untreated patients, the breadth of the anti-core specific T cell response was inversely correlated with serum HBsAg concentrations as well as HBV-DNA and ALT levels and was significantly different in patients with HBsAg levels either above or below 1000 IU/mL. The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients.

Conclusions: Different clinical outcomes of cHBV infection are associated with the magnitude, breadth and specificity of the HBV-specific T cell response. Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control.

Show MeSH
Related in: MedlinePlus