Reviewer’s report  
 
Title: Food IgG4 antibodies are elevated not only in children  with wheat allergy but also in 
children with gastrointestinal diseases  
 
Version: 0 Date: 14 Oct 2015  
 
Reviewer: Carlo caffarelli  
 
Reviewer's report:  
 
The presented manuscript describes a study on IgG4 and IgG levels in children with wheat 
allergy, celiac disease and HP infection. This cross -sectional study is quite interesting. However , 
result section is difficult to follow and additional information should be given to properly assess 
the diagnostic value of IgG levels. There are also some important remarks that need to be 
addressed. English language needs to be revised. Please do not u nderline the text. I have the 
following comments.  
 
 
 
Title. I would suggest Food IgG4 antibodies are elevated not only in children with wheat allergy 
but also in children with gastrointestinal diseases  
 
 
 
1. Methods  
 
- Line 79 .It seems that children with wheat allergy are the same population studied in a 
previous trial (Ref. #8). Authors should state whether this is the case or not.  
 
 
- Line 83. Food challenge. It should be briefly described. Authors may take into 
consideratio n that measurement of blood pressure has been found to be useful for 
interpreting the outcome of food challenges (see Ann Allergy Asthma Immunol 2012 
;108:285 -6). So it would be important to know whether decreased blood pressure was 
recorded during challen ges. A comment in the discussion would be of interest.  
 
 
- Line 83. It wou ld be useful to know which criteria were used to define a positive food 
challenge and which symptoms were elicited.  
 
 
- Line 118. It should be stated when a SPT result to foods was  regarded as positive.  
 
 
 
Results  
 
 
- A new table comparing baseline characteristics (age …) of study groups and healthy 
controls is warranted.  
 
 
- Data on frequency of children with positive IgG4 and IgG should report in the result 
section and in a  new Table. These data are useful for understand their interpretation (Line 
188 and 199).  
 
 
- Data on diagnostic accuracy of IgG4 and IgG should be provided.  
 
 
- Figure 1. It is a chaos. Data of each study group are lacking. There is no indication of 
medi an values. It is unclear which comparison between groups resulted significant 
(p<0.05). The same issues should be clarified in Figures 2, 3, 4.  
 
 
 
Discussion  
 
- It is very long and difficult to follow. It should be shortened.  
 
 
- Line 216. Please consider t hat intestinal permeability is reduced by a restrict diet in 
children with atopic dermatitis (see Clin Exp Allergy. 1993 Jan;23(1):28 -31).  
 
 
- Line 217. "natural" should be deleted.  
 
 
- Authors should take into account both in the introduction and in the conclusions that 
recent papers showed that an atopic antibody response to food allergens involves both 
IgG and IgE. However a non IgE -mediated mechanism such as IgG -mediated is not 
involved in onset of food hypersensitivity reactions as showed by findings on diagnostic 
accuracy of patch test and skin prick test in children with cow's milk allergy (Caglayan 
Sozmen S Pediatr Allergy Immunol 2015,26;416 -422).  
 
 
- In the discussi on, strengths and limitations of the study should be considered according to 
the remarks and requested new data.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes  
 
Does the work  include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes  
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published 
 
Declaration of competing interests  
Please complete a declaration of c ompeting interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either  now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are yo u currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do yo u have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  
If your reply is yes to any, please give details below.  
 
'I declare that I have no competing interests'  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publica tion, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by /4.0/). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
 
Reviewer’s report  
 
Title: Food IgG4 antibodies are elevated not only in children  with wheat allergy but also in 
children with gastrointestinal diseases  
 
Version: 0 Date: 14 Oct 2015  
 
Reviewer: Carlo caffarelli  
 
Reviewer's report:  
 
The presented manuscript describes a study on IgG4 and IgG levels in children with wheat 
allergy, celiac disease and HP infection. This cross -sectional study is quite interesting. However , 
result section is difficult to follow and additional information should be given to properly assess 
the diagnostic value of IgG levels. There are also some important remarks that need to be 
addressed. English language needs to be revised. Please do not u nderline the text. I have the 
following comments.  
 
 
 
Title. I would suggest Food IgG4 antibodies are elevated not only in children with wheat allergy 
but also in children with gastrointestinal diseases  
 
 
 
1. Methods  
 
- Line 79 .It seems that children with wheat allergy are the same population studied in a 
previous trial (Ref. #8). Authors should state whether this is the case or not.  
 
 
- Line 83. Food challenge. It should be briefly described. Authors may take into 
consideratio n that measurement of blood pressure has been found to be useful for 
interpreting the outcome of food challenges (see Ann Allergy Asthma Immunol 2012 
;108:285 -6). So it would be important to know whether decreased blood pressure was 
recorded during challen ges. A comment in the discussion would be of interest.  
 
 
- Line 83. It wou ld be useful to know which criteria were used to define a positive food 
challenge and which symptoms were elicited.  
 
 
- Line 118. It should be stated when a SPT result to foods was  regarded as positive.  
 
 
 
Results  
 
 
- A new table comparing baseline characteristics (age …) of study groups and healthy 
controls is warranted.  
 
 
- Data on frequency of children with positive IgG4 and IgG should report in the result 
section and in a  new Table. These data are useful for understand their interpretation (Line 
188 and 199).  
 
 
- Data on diagnostic accuracy of IgG4 and IgG should be provided.  
 
 
- Figure 1. It is a chaos. Data of each study group are lacking. There is no indication of 
medi an values. It is unclear which comparison between groups resulted significant 
(p<0.05). The same issues should be clarified in Figures 2, 3, 4.  
 
 
 
Discussion  
 
- It is very long and difficult to follow. It should be shortened.  
 
 
- Line 216. Please consider t hat intestinal permeability is reduced by a restrict diet in 
children with atopic dermatitis (see Clin Exp Allergy. 1993 Jan;23(1):28 -31).  
 
 
- Line 217. "natural" should be deleted.  
 
 
- Authors should take into account both in the introduction and in the conclusions that 
recent papers showed that an atopic antibody response to food allergens involves both 
IgG and IgE. However a non IgE -mediated mechanism such as IgG -mediated is not 
involved in onset of food hypersensitivity reactions as showed by findings on diagnostic 
accuracy of patch test and skin prick test in children with cow's milk allergy (Caglayan 
Sozmen S Pediatr Allergy Immunol 2015,26;416 -422).  
 
 
- In the discussi on, strengths and limitations of the study should be considered according to 
the remarks and requested new data.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes  
 
Does the work  include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes  
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published 
 
Declaration of competing interests  
Please complete a declaration of c ompeting interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either  now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are yo u currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do yo u have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  
If your reply is yes to any, please give details below.  
 
'I declare that I have no competing interests'  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publica tion, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by /4.0/). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
 
Please review this paper.
user
Reviewer’s report  
 
Title: Food IgG4 antibodies are elevated not only in children  with wheat allergy but also in 
children with gastrointestinal diseases  
 
Version: 0 Date: 14 Oct 2015  
 
Reviewer: Carlo caffarelli  
 
Reviewer's report:  
 
The presented manuscript describes a study on IgG4 and IgG levels in children with wheat 
allergy, celiac disease and HP infection. This cross -sectional study is quite interesting. However , 
result section is difficult to follow and additional information should be given to properly assess 
the diagnostic value of IgG levels. There are also some important remarks that need to be 
addressed. English language needs to be revised. Please do not u nderline the text. I have the 
following comments.  
 
 
 
Title. I would suggest Food IgG4 antibodies are elevated not only in children with wheat allergy 
but also in children with gastrointestinal diseases  
 
 
 
1. Methods  
 
- Line 79 .It seems that children with wheat allergy are the same population studied in a 
previous trial (Ref. #8). Authors should state whether this is the case or not.  
 
 
- Line 83. Food challenge. It should be briefly described. Authors may take into 
consideratio n that measurement of blood pressure has been found to be useful for 
interpreting the outcome of food challenges (see Ann Allergy Asthma Immunol 2012 
;108:285 -6). So it would be important to know whether decreased blood pressure was 
recorded during challen ges. A comment in the discussion would be of interest.  
 
 
- Line 83. It wou ld be useful to know which criteria were used to define a positive food 
challenge and which symptoms were elicited.  
 
 
- Line 118. It should be stated when a SPT result to foods was  regarded as positive.  
 
 
 
Results  
 
 
- A new table comparing baseline characteristics (age …) of study groups and healthy 
controls is warranted.  
 
 
- Data on frequency of children with positive IgG4 and IgG should report in the result 
section and in a  new Table. These data are useful for understand their interpretation (Line 
188 and 199).  
 
 
- Data on diagnostic accuracy of IgG4 and IgG should be provided.  
 
 
- Figure 1. It is a chaos. Data of each study group are lacking. There is no indication of 
medi an values. It is unclear which comparison between groups resulted significant 
(p<0.05). The same issues should be clarified in Figures 2, 3, 4.  
 
 
 
Discussion  
 
- It is very long and difficult to follow. It should be shortened.  
 
 
- Line 216. Please consider t hat intestinal permeability is reduced by a restrict diet in 
children with atopic dermatitis (see Clin Exp Allergy. 1993 Jan;23(1):28 -31).  
 
 
- Line 217. "natural" should be deleted.  
 
 
- Authors should take into account both in the introduction and in the conclusions that 
recent papers showed that an atopic antibody response to food allergens involves both 
IgG and IgE. However a non IgE -mediated mechanism such as IgG -mediated is not 
involved in onset of food hypersensitivity reactions as showed by findings on diagnostic 
accuracy of patch test and skin prick test in children with cow's milk allergy (Caglayan 
Sozmen S Pediatr Allergy Immunol 2015,26;416 -422).  
 
 
- In the discussi on, strengths and limitations of the study should be considered according to 
the remarks and requested new data.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes  
 
Does the work  include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes  
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published 
 
Declaration of competing interests  
Please complete a declaration of c ompeting interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either  now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are yo u currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do yo u have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  
If your reply is yes to any, please give details below.  
 
'I declare that I have no competing interests'  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publica tion, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by /4.0/). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
 
assistant