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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

Percentage of patients with anti-HBV T cell response to the four HBV proteins in each subgroup.Percentage of patients in each clinical group with at least one response to the four different HBV proteins. Differences between percentage evaluated by Fisher’s exact test* = p value: 0.05. ** = p value: 0.015.
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pone-0065327-g002: Percentage of patients with anti-HBV T cell response to the four HBV proteins in each subgroup.Percentage of patients in each clinical group with at least one response to the four different HBV proteins. Differences between percentage evaluated by Fisher’s exact test* = p value: 0.05. ** = p value: 0.015.

Mentions: Overall, virus-specific T cells response was generally (75% of cases) directed towards more than one peptide and different proteins (i.e. multispecific T cell response) so that the effect of T cell specificity on HBV control could be addressed. Comparing the fine specificities of T cell responses between the four groups showed significantly different response patterns (Figure 2). Across the entire cohort, core and polymerase sequences were significantly more often targeted than X protein and envelope (54%, 67%, 21% and 27% respectively, p<0.01, data not shown). However, the IC group showed a preferential targeting of the HBV core region (85% of IC patients showed at least one anti-core T cell response), which was significantly higher than the core response rates in TC and CHB patients (p = 0.05 and p = 0.015, respectively, Figure 2). In turn, in the TC patients, the antiviral T cell reactivity was mainly directed against the polymerase protein (75% of total response), while the control group of HBV resolvers was characterized by targeting structural viral components (core and envelope), without any responses to the X protein. The response rates to the X-protein were low in the other groups as well, with response detected maximally in one third of tested individuals. Together, these data link different response patterns of the T cell response with distinct clinical outcome of HBV infection and suggest a potentially superior in vivo effectiveness of the Core and Envelope specific T cell activities.


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)

Percentage of patients with anti-HBV T cell response to the four HBV proteins in each subgroup.Percentage of patients in each clinical group with at least one response to the four different HBV proteins. Differences between percentage evaluated by Fisher’s exact test* = p value: 0.05. ** = p value: 0.015.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065327-g002: Percentage of patients with anti-HBV T cell response to the four HBV proteins in each subgroup.Percentage of patients in each clinical group with at least one response to the four different HBV proteins. Differences between percentage evaluated by Fisher’s exact test* = p value: 0.05. ** = p value: 0.015.
Mentions: Overall, virus-specific T cells response was generally (75% of cases) directed towards more than one peptide and different proteins (i.e. multispecific T cell response) so that the effect of T cell specificity on HBV control could be addressed. Comparing the fine specificities of T cell responses between the four groups showed significantly different response patterns (Figure 2). Across the entire cohort, core and polymerase sequences were significantly more often targeted than X protein and envelope (54%, 67%, 21% and 27% respectively, p<0.01, data not shown). However, the IC group showed a preferential targeting of the HBV core region (85% of IC patients showed at least one anti-core T cell response), which was significantly higher than the core response rates in TC and CHB patients (p = 0.05 and p = 0.015, respectively, Figure 2). In turn, in the TC patients, the antiviral T cell reactivity was mainly directed against the polymerase protein (75% of total response), while the control group of HBV resolvers was characterized by targeting structural viral components (core and envelope), without any responses to the X protein. The response rates to the X-protein were low in the other groups as well, with response detected maximally in one third of tested individuals. Together, these data link different response patterns of the T cell response with distinct clinical outcome of HBV infection and suggest a potentially superior in vivo effectiveness of the Core and Envelope specific T cell activities.

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