Reviewer ’s report  
 
Title:  Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, 
risk of intestinal stricture in Crohn's disease, and clini cal prognosis in inflammatory bowel 
disease  
 
Version: 0 Date: 25 Feb 2017 
 
Reviewer:  Doron  Yablecovitch  
 
Reviewer’s report:  
 
 > The manuscript by Tran et al. investigates serum levels of cathelicidin for suitability as a 
potential biomarker in patients with IBD. The authors demonstrate that serum levels of 
cathelicidin, as determined by ELISA, are inve rsely correlated with clinical indices in patients 
IBD. They report that high levels of cathelicidin may suggest a better prognosis in IBD patients 
and that low levels of cathelicidin is a predictor of fibrostenotic disease.  The point of the study 
is very  interesting because of the increasing attention on non -invasive biomarkers that could 
confirm the diagnosis of IBD or help to monitoring disease activity and severity. A major 
strength of this study is its novelty, particularly given the paucity data rega rding circulating 
cathelicidin in IBD.  
 
The results are therefore of potential interest to the readers of BMC Gastroenterology  
 
 
However, the manuscript could benefit from some revisions, as outlined below:  
 
- Introduction - More details are needed regar ding to the structure and the expression of 
cathelicidin. Please add a brief paragraph about cathelicidin molecular structure and cellular 
source. It would be helpful to mention recent studies considering vitamin D and cathelicidin 
expression  
 
-Material a nd Methods - lines 24 -37:  The paragraph fits better in the introduction.  
 
- Line 44 - Please change "Cohort 1 and 2" to "Patients and samples"  
 
-Line 59 - Power analysis should be integrated to the statistical analysis section.  
. 
Results - Line 22 (P.8) please provide the standard deviation or the SEM of chathelicidin levels 
in UC, CD patients and healthy controls  
 
Line 31 (P.8) - Please provide the correlation coefficient regarding cathelicidin levels  
and UC clinical activity.  
 
Lines 5 -31 (P.9) Please  replace "prognosis" to "future clinical activity".  
 
Lines 39 -41 (P.9) The addition of p values between the different mayo endoscopic score 
subgroups is recommended.  
 
Line 12 (P.10) Please replace 'clinical prognosis" to "future clinical activity"  
 
Line 14  (P.10) Please provide the correlation coefficient  
 
Discussion - Line 22 -" The cellular source of cathelicidin in IBD is not known" this is incorrect 
and should be rephrased  
 
Addition of a comment regarding the role of cathelicidin in fibrogenesis in inflammatory bowel 
disease is recommended.  
 
The study by Schauber should be discussed as it describes no statistical difference in cathelicidin 
expression in Crohn's disease compar e to healthy controls  
 
It would be appropriate to discuss potential advantages of this biomarker (if any), in comparison 
with other conventional inflammatory markers.  
 
Lines 12 -22 (P.14) The paragraph does not fit the discussion section.  
 
Line 47 (P.14) "I t can  also serve as an independent…"  I recommend toning down that 
conclusion.  
  
Please discuss the potential advantage of cathelicidin as a novel therapeutic strategy in IBD.  
 
- Table 1 please considers a more clear presentation of the data. Definitio n of the abbreviation is 
needed.  
 
General  
 
- Please recheck the reference numbering because there seems to be some inaccuracies.   
 
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.  
 
No 
 
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:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing 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 o r lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you 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 you 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 publication, 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 ma de 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 c an 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:  Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, 
risk of intestinal stricture in Crohn's disease, and clini cal prognosis in inflammatory bowel 
disease  
 
Version: 0 Date: 25 Feb 2017 
 
Reviewer:  Doron  Yablecovitch  
 
Reviewer’s report:  
 
 > The manuscript by Tran et al. investigates serum levels of cathelicidin for suitability as a 
potential biomarker in patients with IBD. The authors demonstrate that serum levels of 
cathelicidin, as determined by ELISA, are inve rsely correlated with clinical indices in patients 
IBD. They report that high levels of cathelicidin may suggest a better prognosis in IBD patients 
and that low levels of cathelicidin is a predictor of fibrostenotic disease.  The point of the study 
is very  interesting because of the increasing attention on non -invasive biomarkers that could 
confirm the diagnosis of IBD or help to monitoring disease activity and severity. A major 
strength of this study is its novelty, particularly given the paucity data rega rding circulating 
cathelicidin in IBD.  
 
The results are therefore of potential interest to the readers of BMC Gastroenterology  
 
 
However, the manuscript could benefit from some revisions, as outlined below:  
 
- Introduction - More details are needed regar ding to the structure and the expression of 
cathelicidin. Please add a brief paragraph about cathelicidin molecular structure and cellular 
source. It would be helpful to mention recent studies considering vitamin D and cathelicidin 
expression  
 
-Material a nd Methods - lines 24 -37:  The paragraph fits better in the introduction.  
 
- Line 44 - Please change "Cohort 1 and 2" to "Patients and samples"  
 
-Line 59 - Power analysis should be integrated to the statistical analysis section.  
. 
Results - Line 22 (P.8) please provide the standard deviation or the SEM of chathelicidin levels 
in UC, CD patients and healthy controls  
 
Line 31 (P.8) - Please provide the correlation coefficient regarding cathelicidin levels  
and UC clinical activity.  
 
Lines 5 -31 (P.9) Please  replace "prognosis" to "future clinical activity".  
 
Lines 39 -41 (P.9) The addition of p values between the different mayo endoscopic score 
subgroups is recommended.  
 
Line 12 (P.10) Please replace 'clinical prognosis" to "future clinical activity"  
 
Line 14  (P.10) Please provide the correlation coefficient  
 
Discussion - Line 22 -" The cellular source of cathelicidin in IBD is not known" this is incorrect 
and should be rephrased  
 
Addition of a comment regarding the role of cathelicidin in fibrogenesis in inflammatory bowel 
disease is recommended.  
 
The study by Schauber should be discussed as it describes no statistical difference in cathelicidin 
expression in Crohn's disease compar e to healthy controls  
 
It would be appropriate to discuss potential advantages of this biomarker (if any), in comparison 
with other conventional inflammatory markers.  
 
Lines 12 -22 (P.14) The paragraph does not fit the discussion section.  
 
Line 47 (P.14) "I t can  also serve as an independent…"  I recommend toning down that 
conclusion.  
  
Please discuss the potential advantage of cathelicidin as a novel therapeutic strategy in IBD.  
 
- Table 1 please considers a more clear presentation of the data. Definitio n of the abbreviation is 
needed.  
 
General  
 
- Please recheck the reference numbering because there seems to be some inaccuracies.   
 
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.  
 
No 
 
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:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing 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 o r lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you 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 you 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 publication, 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 ma de 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 c an 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:  Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, 
risk of intestinal stricture in Crohn's disease, and clini cal prognosis in inflammatory bowel 
disease  
 
Version: 0 Date: 25 Feb 2017 
 
Reviewer:  Doron  Yablecovitch  
 
Reviewer’s report:  
 
 > The manuscript by Tran et al. investigates serum levels of cathelicidin for suitability as a 
potential biomarker in patients with IBD. The authors demonstrate that serum levels of 
cathelicidin, as determined by ELISA, are inve rsely correlated with clinical indices in patients 
IBD. They report that high levels of cathelicidin may suggest a better prognosis in IBD patients 
and that low levels of cathelicidin is a predictor of fibrostenotic disease.  The point of the study 
is very  interesting because of the increasing attention on non -invasive biomarkers that could 
confirm the diagnosis of IBD or help to monitoring disease activity and severity. A major 
strength of this study is its novelty, particularly given the paucity data rega rding circulating 
cathelicidin in IBD.  
 
The results are therefore of potential interest to the readers of BMC Gastroenterology  
 
 
However, the manuscript could benefit from some revisions, as outlined below:  
 
- Introduction - More details are needed regar ding to the structure and the expression of 
cathelicidin. Please add a brief paragraph about cathelicidin molecular structure and cellular 
source. It would be helpful to mention recent studies considering vitamin D and cathelicidin 
expression  
 
-Material a nd Methods - lines 24 -37:  The paragraph fits better in the introduction.  
 
- Line 44 - Please change "Cohort 1 and 2" to "Patients and samples"  
 
-Line 59 - Power analysis should be integrated to the statistical analysis section.  
. 
Results - Line 22 (P.8) please provide the standard deviation or the SEM of chathelicidin levels 
in UC, CD patients and healthy controls  
 
Line 31 (P.8) - Please provide the correlation coefficient regarding cathelicidin levels  
and UC clinical activity.  
 
Lines 5 -31 (P.9) Please  replace "prognosis" to "future clinical activity".  
 
Lines 39 -41 (P.9) The addition of p values between the different mayo endoscopic score 
subgroups is recommended.  
 
Line 12 (P.10) Please replace 'clinical prognosis" to "future clinical activity"  
 
Line 14  (P.10) Please provide the correlation coefficient  
 
Discussion - Line 22 -" The cellular source of cathelicidin in IBD is not known" this is incorrect 
and should be rephrased  
 
Addition of a comment regarding the role of cathelicidin in fibrogenesis in inflammatory bowel 
disease is recommended.  
 
The study by Schauber should be discussed as it describes no statistical difference in cathelicidin 
expression in Crohn's disease compar e to healthy controls  
 
It would be appropriate to discuss potential advantages of this biomarker (if any), in comparison 
with other conventional inflammatory markers.  
 
Lines 12 -22 (P.14) The paragraph does not fit the discussion section.  
 
Line 47 (P.14) "I t can  also serve as an independent…"  I recommend toning down that 
conclusion.  
  
Please discuss the potential advantage of cathelicidin as a novel therapeutic strategy in IBD.  
 
- Table 1 please considers a more clear presentation of the data. Definitio n of the abbreviation is 
needed.  
 
General  
 
- Please recheck the reference numbering because there seems to be some inaccuracies.   
 
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.  
 
No 
 
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:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing 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 o r lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you 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 you 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 publication, 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 ma de 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 c an 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