Serum Concentrations of Antigen-Specific IgG4 in Patients with Japanese Cedar Pollinosis

Round 1

Reviewer 1 Report

The manuscript “Serum concentrations of antigen specific IgG4 in patients with 2 Japanese cedar pollinosis.” is well relative well-written and discussed.

However, follow some considerations so that the authors can use them in order to improve the article.

1. The state of the art should be improved, and more references should be included.
2. 1. Patients. Please insert the maximum and minimum of ages, you only reported the average age, being important to know the age interval. Additionally, it´s important to include more information used to create the three different groups.
3. Results and discussion. The discussion of the results should be improved. The results need to be compared with more references. Additionally, other information should be included, in order to increase the quality of the manuscript.

Author Response

Reviewer #1:

1. The state of the art should be improved, and more references should be included.

Thank you for your useful comments and suggestions.  According to the suggestions, the state of the Figures has been changed and the number of references was increased. 

2. The more information about the patients including the maximum and minimum of ages should be reported.  Additionally, more the details to create the three different groups should be stated.  

Thank you for your useful comments and suggestions.  According to the suggestions, the more details of the information were added.

3. The discussion of the results should be improved.  The results need to be compared with more references.  Additionally, other information should be included in order to increase the quality of the manuscript. 

Thank you for your useful comments and suggestions.  According to the suggestions, the more details of the information was added.

Reviewer 2 Report

Kitaya and co studies levels of serum levels of IgE, IgG, IgG4 in patients with Japanese cedar polinosis (JCP) grouped into 3 categories by allergen immunotherapy treatment delivery (subcutaneous/SCIT, or sublingual/SLIT) and outcome (“Successful” or otherwise/”Unsatisfactory”): SCIT (N=13), SLIT Successful (N=16), SLIT Unsatisfactory (N=76).  The patients appear to be from 2 distinct sites Shiga (south central Honshu), and Tohoku (north Honshu) with distinct Köppen climate classification and phenology. The authors claim IgG4 to be correlated with clinical response to SLIT.

Below are my 6 major concerns – mainly regarding study design and result interpretation.

[1] Lines 72-76: The 3 categories are poorly defined especially “SLIT Unsatisfactory”, and “SLIT Successful” is a misleading label - and one cannot properly understand if their comparisons are interpretable. They define “SLIT Successful” (N=16) as subjects treated by SCIT or SLIT only (not SLIT alone, despite the name of category), who were able to control symptoms without antiallergic rescue agents, whereas “SLIT Unsatisfactory” (N=76) are subjects where treatment with SLIT (only?) was not sufficiently effective. No information about whether SCIT was eventually given to “SLIT Unsatisfactory” subjects (or outcome from that). The “SLIT Successful” category should be more properly renamed “SLIT or SCIT Successful”.

[2] There should be a table tallying the N=16 subjects in “SLIT Successful” category who responded to SLIT alone, and/or to SCIT alone.

[3] Line 81: Please state the date/time interval “collected during the high season of JC pollen release in 2015”. Is this on line 67?

[4] There should be a table of sex, age, site (Shiga vs Tohoku) and other potential confounding factors for each of the 3 categories. Is there significant difference in sex, age, site across between the 3 categories? I am particularly concerned about the difference in site being a confounding factor.

[5] Line 146 is misleading: This line should properly read - IgG4 is significantly correlated with clinical efficacy of SCIT or SLIT (not SLIT alone), because of the authors definition of subjects in “SLIT Successful” category.

[6] The Abstract should indicate the very important matter of how the authors defined “SLIT Successful”.

Author Response

Reviewers' comments:

Before considering this manuscript for final acceptance, I have some revisions to suggest.  

1．First of all, I think that the author should detail the two groups demographic characteristics with special attention to those comorbidities which could influence the results in case some difference was found between populations.  Providing one table for this is highy recommended. 

Thank you for your useful comments and suggestions.  I added another table in my manuscript according to your comments and suggestions. 

2. Secondly, the treatment allocation method should be specified.

Thank you for your useful comments and suggestions. The treatment allocation method was specified.  

3. An English native check is recommended.

 Thank you for your useful comments and suggestions.  An English native check has been completed before submission. 

Reviewer 3 Report

Dear Author,

I found your manuscript very interesting, with the advantage of discussing a complex subject in a clear and synthetic way.

Although there are some explicitated limits: the retrospective study design, the small cohorts and the impaired treatment period of the two groups, this manuscritp can inspire further studies to confirm its results.

Before considering it for final acceptance, I have some revisions to suggest.

First of all, I think that the author should detail the two groups demographic characteriscs with special attention to those comorbidities which could influence the results in case some difference was found between populations. Providing one table for this is highly recommended.

Secondly, the treatment allocation method should be specified.

I also recommend an English revision before further submission and a full text control to avoid repetitions (e.g.: the last sentence of the "conclusion" paragraph and the first sentence of the "discussion" paragraph.

Author Response

Reviewers' comments:

The author claim IgG4 to be correlated with clinical response to SLIT.  Below are my 6 major concerns –mainly regarding study design and result interpretation. 

1. The 3 categories are poorly defined especially “SLIT Unsatisfactory”, and “SLIT Successful” is a misleading label- and one cannot properly understand if their comparisons are interpretable. They define “SLIT Successful” (N=16) as subjects treated by SCIT or SLIT only (not SLIT alone, despite the name of category), who were able to control symptoms without antiallergic rescue agents, whereas “SLIT Unsatisfactory” (N=76) are subjects where treatment with SLIT was not sufficiently effective. No information about whether SCIT was eventually given to “SLIT Unsatisfactory” subjects (or outcome from that).  The “SLIT Successful” catergory should be more properly renamed ”SLIT or SCIT Successful ”. 

Thank you for your useful comments and suggestions.  I revised the Abstract according to your comments and suggestions as follows.   

2. There should be a table regarding the N-16 sugjects in “SLIT Successful” category who responded to SLIT alone, and/or to SCIT alone.

Thank you for your useful comments and suggestions.  I added another table in my manuscript according to your comments and suggestions.

3. Please state the date/time interval “collected during the high season of JC pollen release in 2015”.

Thank you for your useful comments and suggestions.  I added the information about pollen release in my manuscript according to your comments and suggestions.

4. There should be a table of sex, age, site and other potential confounding factors for each of the 3 categories. Is there significant difference in sex, age, site across between the 3 categories? I am particularly concerned about the difference in site being a confounding factor.   

Thank you for your useful comments and suggestions.  I added another table in my manuscript according to your comments and suggestions.

5. Line 146 is misleading: This line should properly read- IgG4 is significantly correlated with clinical efficacy of SCIT or SLIT (not SLIT alone), because of the authors definition of subjects in “SLIT Successful” category.

Thank you for your useful comments and suggestions.  I revised the Abstract according to your comments and suggestions as follows.

6. The Abstract should indicate the very important matter of how the authors defined “SLIT successful”.

Thank you for your useful comments and suggestions.  I revised the Abstract according to your comments and suggestions as follows.