Reviewer's report
Title:Changes of Treg andTh17 balance in the development of acute and
chronic HBV infection
Version: 2Date:30 January 2012
Reviewer: Christoph Neumann-Haefelin
Reviewer's report:
Xue-Song et al. study the impact of Treg and Th17 balance in the course of HBV
infection. Their findings are largely confirmative when compared to recent studies
(e.g., Zhang et al., Hepatology 2010, 51:81-91; Zhai et al., Viral Immunol 2011,
24:303-10; Niu et al., BMC Immunol 2011, 19;12:47). Most importantly, the
correlation of Th17 cells with ALT levels and increased frequency of Th17 cells
as well as the decreased Treg:Th17 ratio have been described previously.
In addition, there are several discrepancies and other issues in the study that
need to be addressed.
Major:
- The abstract needs to be better organized. In particular, the methods section
should introduce the different patient groups studied and also introduce the
abbreviation used later (CHB, ACHBLF etc.). Unspecific terms such as “acute
liver inflammation” and “chronic inflammation” should be avoided, and the
specific patient groups should be stated in the results section.
- Introduction section: previous findings regarding Th17 cells and the Treg:Th17
ratio need to be explained in more detail in order to indicate that purpose and
significance of the study.
- The authors find increased Th17 cytokine profiles in acute hepatitis B (AHB)
and acute-on-chronic hepatitis B liver failure (ACHBLF) patients, but increased
Treg cytokine profiles in chronic hepatitis B (CHB) patients. This finding is not
consistent, however, with the significantly reduced Treg:Th17 cell ratio in both,
ACHBLF as well as CHB patients (Fig. 2d). Therefore, the conclusion that “CHB
patients showed too strong Treg cell-mediated immunity and ACHBLF patients
showed too strong Th17 cell-mediated immunity” (page 6), or, similarly,
“Immunosuppression by Treg cells mainly occurs in CHB and Th17-mediated
inflammatory damage mianly occurs in ACHBLF” (page 7) is not strongly
supported by the data presented.
- In Figure 3, the authors include all patient groups in their correlation of
immunological parameters with clinical parameters. This is not suitable, since the
patient cohorts show a clear clustering in these analysis (e.g., the acute hepatitis
B cohort clusters due to their high ALT levels in Fig. 3a+c, while the
acute-on-chronic hepatitis B liver failure cohort clusters due to high total bilirubin
levels in Fig. 3b+d+g.). Thus, separate analysis for the individual patient cohorts
are necessary.
- The authors find an inverse correlation of Th17 cells and viral load, which is in
contrast to the findings of Zhang et al. (Hepatology 2010, 51:81-91). This needs
to be discussed.
- Original data, most important dot blots of intracellular IL-17 and Foxp3 stainings
need to be displayed.
- The manuscript needs revision by a native scientist. For example, the authors
often used “were correlated” instead of “did not correlate with”.
Minor.
- page numbers are missing.
- “Tbil” is not a usual abbreviation and should be replaced by total bilirubin in the
abstract and manuscript.
- Page 3: “More than 20 billion people have been infected with HBV globally...”: Is
this a estimation of people infected in history? I did not find this number in the
references given (refs 1 and 2).
- Page 3: “In chronic hepatitis B (CHB), Foxp3+ Treg cells are closely related with
the development and progress of the disease (refs 10-12).”: Ref 11 does not deal
with HBV.
- Page 4: Il-2 is not a good Treg marker.
- Page 4 and Figure 2d: Treg/Th17 ratio is a pure number, not a percent value.
- Page 5 : Which “liver inflammation indexes” were used? Were these based on
serological markers or histology?
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Changes of Treg andTh17 balance in the development of acute and
chronic HBV infection
Version: 2Date:30 January 2012
Reviewer: Christoph Neumann-Haefelin
Reviewer's report:
Xue-Song et al. study the impact of Treg and Th17 balance in the course of HBV
infection. Their findings are largely confirmative when compared to recent studies
(e.g., Zhang et al., Hepatology 2010, 51:81-91; Zhai et al., Viral Immunol 2011,
24:303-10; Niu et al., BMC Immunol 2011, 19;12:47). Most importantly, the
correlation of Th17 cells with ALT levels and increased frequency of Th17 cells
as well as the decreased Treg:Th17 ratio have been described previously.
In addition, there are several discrepancies and other issues in the study that
need to be addressed.
Major:
- The abstract needs to be better organized. In particular, the methods section
should introduce the different patient groups studied and also introduce the
abbreviation used later (CHB, ACHBLF etc.). Unspecific terms such as “acute
liver inflammation” and “chronic inflammation” should be avoided, and the
specific patient groups should be stated in the results section.
- Introduction section: previous findings regarding Th17 cells and the Treg:Th17
ratio need to be explained in more detail in order to indicate that purpose and
significance of the study.
- The authors find increased Th17 cytokine profiles in acute hepatitis B (AHB)
and acute-on-chronic hepatitis B liver failure (ACHBLF) patients, but increased
Treg cytokine profiles in chronic hepatitis B (CHB) patients. This finding is not
consistent, however, with the significantly reduced Treg:Th17 cell ratio in both,
ACHBLF as well as CHB patients (Fig. 2d). Therefore, the conclusion that “CHB
patients showed too strong Treg cell-mediated immunity and ACHBLF patients
showed too strong Th17 cell-mediated immunity” (page 6), or, similarly,
“Immunosuppression by Treg cells mainly occurs in CHB and Th17-mediated
inflammatory damage mianly occurs in ACHBLF” (page 7) is not strongly
supported by the data presented.
- In Figure 3, the authors include all patient groups in their correlation of
immunological parameters with clinical parameters. This is not suitable, since the
patient cohorts show a clear clustering in these analysis (e.g., the acute hepatitis
B cohort clusters due to their high ALT levels in Fig. 3a+c, while the
acute-on-chronic hepatitis B liver failure cohort clusters due to high total bilirubin
levels in Fig. 3b+d+g.). Thus, separate analysis for the individual patient cohorts
are necessary.
- The authors find an inverse correlation of Th17 cells and viral load, which is in
contrast to the findings of Zhang et al. (Hepatology 2010, 51:81-91). This needs
to be discussed.
- Original data, most important dot blots of intracellular IL-17 and Foxp3 stainings
need to be displayed.
- The manuscript needs revision by a native scientist. For example, the authors
often used “were correlated” instead of “did not correlate with”.
Minor.
- page numbers are missing.
- “Tbil” is not a usual abbreviation and should be replaced by total bilirubin in the
abstract and manuscript.
- Page 3: “More than 20 billion people have been infected with HBV globally...”: Is
this a estimation of people infected in history? I did not find this number in the
references given (refs 1 and 2).
- Page 3: “In chronic hepatitis B (CHB), Foxp3+ Treg cells are closely related with
the development and progress of the disease (refs 10-12).”: Ref 11 does not deal
with HBV.
- Page 4: Il-2 is not a good Treg marker.
- Page 4 and Figure 2d: Treg/Th17 ratio is a pure number, not a percent value.
- Page 5 : Which “liver inflammation indexes” were used? Were these based on
serological markers or histology?
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Changes of Treg andTh17 balance in the development of acute and
chronic HBV infection
Version: 2Date:30 January 2012
Reviewer: Christoph Neumann-Haefelin
Reviewer's report:
Xue-Song et al. study the impact of Treg and Th17 balance in the course of HBV
infection. Their findings are largely confirmative when compared to recent studies
(e.g., Zhang et al., Hepatology 2010, 51:81-91; Zhai et al., Viral Immunol 2011,
24:303-10; Niu et al., BMC Immunol 2011, 19;12:47). Most importantly, the
correlation of Th17 cells with ALT levels and increased frequency of Th17 cells
as well as the decreased Treg:Th17 ratio have been described previously.
In addition, there are several discrepancies and other issues in the study that
need to be addressed.
Major:
- The abstract needs to be better organized. In particular, the methods section
should introduce the different patient groups studied and also introduce the
abbreviation used later (CHB, ACHBLF etc.). Unspecific terms such as “acute
liver inflammation” and “chronic inflammation” should be avoided, and the
specific patient groups should be stated in the results section.
- Introduction section: previous findings regarding Th17 cells and the Treg:Th17
ratio need to be explained in more detail in order to indicate that purpose and
significance of the study.
- The authors find increased Th17 cytokine profiles in acute hepatitis B (AHB)
and acute-on-chronic hepatitis B liver failure (ACHBLF) patients, but increased
Treg cytokine profiles in chronic hepatitis B (CHB) patients. This finding is not
consistent, however, with the significantly reduced Treg:Th17 cell ratio in both,
ACHBLF as well as CHB patients (Fig. 2d). Therefore, the conclusion that “CHB
patients showed too strong Treg cell-mediated immunity and ACHBLF patients
showed too strong Th17 cell-mediated immunity” (page 6), or, similarly,
“Immunosuppression by Treg cells mainly occurs in CHB and Th17-mediated
inflammatory damage mianly occurs in ACHBLF” (page 7) is not strongly
supported by the data presented.
- In Figure 3, the authors include all patient groups in their correlation of
immunological parameters with clinical parameters. This is not suitable, since the
patient cohorts show a clear clustering in these analysis (e.g., the acute hepatitis
B cohort clusters due to their high ALT levels in Fig. 3a+c, while the
acute-on-chronic hepatitis B liver failure cohort clusters due to high total bilirubin
levels in Fig. 3b+d+g.). Thus, separate analysis for the individual patient cohorts
are necessary.
- The authors find an inverse correlation of Th17 cells and viral load, which is in
contrast to the findings of Zhang et al. (Hepatology 2010, 51:81-91). This needs
to be discussed.
- Original data, most important dot blots of intracellular IL-17 and Foxp3 stainings
need to be displayed.
- The manuscript needs revision by a native scientist. For example, the authors
often used “were correlated” instead of “did not correlate with”.
Minor.
- page numbers are missing.
- “Tbil” is not a usual abbreviation and should be replaced by total bilirubin in the
abstract and manuscript.
- Page 3: “More than 20 billion people have been infected with HBV globally...”: Is
this a estimation of people infected in history? I did not find this number in the
references given (refs 1 and 2).
- Page 3: “In chronic hepatitis B (CHB), Foxp3+ Treg cells are closely related with
the development and progress of the disease (refs 10-12).”: Ref 11 does not deal
with HBV.
- Page 4: Il-2 is not a good Treg marker.
- Page 4 and Figure 2d: Treg/Th17 ratio is a pure number, not a percent value.
- Page 5 : Which “liver inflammation indexes” were used? Were these based on
serological markers or histology?
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
assistant