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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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HBV specific T cell response and HBV serovirological markers in treated patients.A) Correlation between the breadth of the HBV specific T cell response (number of targeted peptides) and HBsAg serum levels (IU/mL) in the 16 treatment-suppressed patients. B) Correlation between breadth of the HBV specific T cell response and HBV-DNA serum levels (IU/mL). For A) and B), Regression line, r coefficient and p value (Spearman Ranks test) are shown. HBV-DNA axis in logarithmic scale. C) Number of responses in the 16 treated patients, stratified by level of HBsAg antigenemia (<1000 and >1000 IU/mL). Each symbol represents an individual patient with bars representing the median per group. * = p value: 0.03 (Mann Whitney).
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pone-0065327-g004: HBV specific T cell response and HBV serovirological markers in treated patients.A) Correlation between the breadth of the HBV specific T cell response (number of targeted peptides) and HBsAg serum levels (IU/mL) in the 16 treatment-suppressed patients. B) Correlation between breadth of the HBV specific T cell response and HBV-DNA serum levels (IU/mL). For A) and B), Regression line, r coefficient and p value (Spearman Ranks test) are shown. HBV-DNA axis in logarithmic scale. C) Number of responses in the 16 treated patients, stratified by level of HBsAg antigenemia (<1000 and >1000 IU/mL). Each symbol represents an individual patient with bars representing the median per group. * = p value: 0.03 (Mann Whitney).

Mentions: In order to assess the impact of antiviral treatment on cellular host immunity to HBV, a group of long-term treated, virally suppressed patients was also evaluated. The duration of treatment was 108 months in median (range 31−132 months). As in the untreated population, HBsAg serum levels were inversely correlated with the overall breadth of virus-specific T responses (r = −0539, p = 0.031, Figure 4A) and, in particular, with the anti-core specific T cell response (r = −0.553, p = 0.026, Figure 4B), although the major contribution to the antiviral reactivity in this group was conferred by anti-polymerase response (Figure 2). Furthermore, dividing the patients on the basis of the above HBsAg cut-off (1000 IU/mL), both the overall breadth of response as well as the anti-core immune response alone were significantly higher in patients with lower antigenemia (median frequency 5,5 vs 3, respectively, p = 0.03, Figure 4C and data not shown). No difference in total or core-specific responses were noted when the treated individuals were stratified for the duration of treatment (<100> months). These data indicate a surprisingly robust maintenance of HBV-specific responses for extended period of time after long-term viral suppression.


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)

HBV specific T cell response and HBV serovirological markers in treated patients.A) Correlation between the breadth of the HBV specific T cell response (number of targeted peptides) and HBsAg serum levels (IU/mL) in the 16 treatment-suppressed patients. B) Correlation between breadth of the HBV specific T cell response and HBV-DNA serum levels (IU/mL). For A) and B), Regression line, r coefficient and p value (Spearman Ranks test) are shown. HBV-DNA axis in logarithmic scale. C) Number of responses in the 16 treated patients, stratified by level of HBsAg antigenemia (<1000 and >1000 IU/mL). Each symbol represents an individual patient with bars representing the median per group. * = p value: 0.03 (Mann Whitney).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065327-g004: HBV specific T cell response and HBV serovirological markers in treated patients.A) Correlation between the breadth of the HBV specific T cell response (number of targeted peptides) and HBsAg serum levels (IU/mL) in the 16 treatment-suppressed patients. B) Correlation between breadth of the HBV specific T cell response and HBV-DNA serum levels (IU/mL). For A) and B), Regression line, r coefficient and p value (Spearman Ranks test) are shown. HBV-DNA axis in logarithmic scale. C) Number of responses in the 16 treated patients, stratified by level of HBsAg antigenemia (<1000 and >1000 IU/mL). Each symbol represents an individual patient with bars representing the median per group. * = p value: 0.03 (Mann Whitney).
Mentions: In order to assess the impact of antiviral treatment on cellular host immunity to HBV, a group of long-term treated, virally suppressed patients was also evaluated. The duration of treatment was 108 months in median (range 31−132 months). As in the untreated population, HBsAg serum levels were inversely correlated with the overall breadth of virus-specific T responses (r = −0539, p = 0.031, Figure 4A) and, in particular, with the anti-core specific T cell response (r = −0.553, p = 0.026, Figure 4B), although the major contribution to the antiviral reactivity in this group was conferred by anti-polymerase response (Figure 2). Furthermore, dividing the patients on the basis of the above HBsAg cut-off (1000 IU/mL), both the overall breadth of response as well as the anti-core immune response alone were significantly higher in patients with lower antigenemia (median frequency 5,5 vs 3, respectively, p = 0.03, Figure 4C and data not shown). No difference in total or core-specific responses were noted when the treated individuals were stratified for the duration of treatment (<100> months). These data indicate a surprisingly robust maintenance of HBV-specific responses for extended period of time after long-term viral suppression.

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