Reviewer ’s report  
 
Title: Case report on pathogenetic link between gluten and IgA nephropathy  
 
Version: 0 Date: 21 Nov 2017  
 
Reviewer: Laureline Berthelot  
 
Reviewer's report:  
 
This manuscript described a case report of a man with cystic f ibrosis who developed IgA 
nephropathy. They treated the patient with steroids, this therapy was efficient to decrease the IgA 
nephropathy symptoms. As IgA nephropathy could be associated with celiac disease and the 
patient exhibited dyspepsia, the authors explored a duodenal biopsy. Interestingly, at the first 
presentation, the morphology was normal but TG2 deposits were present as in the renal biopsy. 
After one year, a new biopsy of intestine was performed showing this time morphological 
changes and abnorm alities.  
 
Major points:  
- This case report is very interesting, but do not support the conclusion. This is not the first 
case report with patient suffering with IgAN and a gluten involvement. Several case reports 
showed that a gluten diet ameliorates the r enal symptoms (Koivuviita N et al 2009 NDT, La 
Villa G et al 2003 W J Gastroenterol, Woodrow G et al 1993 NDT) and two studies, one is 
cited in this article (Coppo et al 1990 Clin Nephrol, Yagame M et al 1988 nephron) 
described the changes in gluten diet a nd their influence on IgAN patients. Moreover, in this 
case report, it is only an association between TG2 presence in the intestine and IgAN, so 
gluten could participate or not. What happens after the gluten diet? The major effect on 
IgAN is due to steroid s in this case report. The title and the conclusion are overstated and 
should be reformulated.  
 
- The authors did not discuss the association between cystic fibrosis and celiac disease.  
 
- "Monteiro et al showed as activation of TG2 is crucial for the depos ition of immune -
complexes" ref 12 is wrong. The pathological role of TG2 in IgAN was shown in Berthelot 
et al J Exp Med 2012. Lechner et al JASN 2016 showed that the removal of IgA deposits 
leaded to the decrease of TG2 staining.  
 
- The role of gluten in a nimal models of IgAN was also shown in Papista et al Kidney Int 
2015 and not only in the article Coppo et al JASN 1992.   
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 requ ire 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 or 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 re lating 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 intere sts? 
 
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 at tachments 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: Case report on pathogenetic link between gluten and IgA nephropathy  
 
Version: 0 Date: 21 Nov 2017  
 
Reviewer: Laureline Berthelot  
 
Reviewer's report:  
 
This manuscript described a case report of a man with cystic f ibrosis who developed IgA 
nephropathy. They treated the patient with steroids, this therapy was efficient to decrease the IgA 
nephropathy symptoms. As IgA nephropathy could be associated with celiac disease and the 
patient exhibited dyspepsia, the authors explored a duodenal biopsy. Interestingly, at the first 
presentation, the morphology was normal but TG2 deposits were present as in the renal biopsy. 
After one year, a new biopsy of intestine was performed showing this time morphological 
changes and abnorm alities.  
 
Major points:  
- This case report is very interesting, but do not support the conclusion. This is not the first 
case report with patient suffering with IgAN and a gluten involvement. Several case reports 
showed that a gluten diet ameliorates the r enal symptoms (Koivuviita N et al 2009 NDT, La 
Villa G et al 2003 W J Gastroenterol, Woodrow G et al 1993 NDT) and two studies, one is 
cited in this article (Coppo et al 1990 Clin Nephrol, Yagame M et al 1988 nephron) 
described the changes in gluten diet a nd their influence on IgAN patients. Moreover, in this 
case report, it is only an association between TG2 presence in the intestine and IgAN, so 
gluten could participate or not. What happens after the gluten diet? The major effect on 
IgAN is due to steroid s in this case report. The title and the conclusion are overstated and 
should be reformulated.  
 
- The authors did not discuss the association between cystic fibrosis and celiac disease.  
 
- "Monteiro et al showed as activation of TG2 is crucial for the depos ition of immune -
complexes" ref 12 is wrong. The pathological role of TG2 in IgAN was shown in Berthelot 
et al J Exp Med 2012. Lechner et al JASN 2016 showed that the removal of IgA deposits 
leaded to the decrease of TG2 staining.  
 
- The role of gluten in a nimal models of IgAN was also shown in Papista et al Kidney Int 
2015 and not only in the article Coppo et al JASN 1992.   
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 requ ire 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 or 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 re lating 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 intere sts? 
 
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 at tachments 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: Case report on pathogenetic link between gluten and IgA nephropathy  
 
Version: 0 Date: 21 Nov 2017  
 
Reviewer: Laureline Berthelot  
 
Reviewer's report:  
 
This manuscript described a case report of a man with cystic f ibrosis who developed IgA 
nephropathy. They treated the patient with steroids, this therapy was efficient to decrease the IgA 
nephropathy symptoms. As IgA nephropathy could be associated with celiac disease and the 
patient exhibited dyspepsia, the authors explored a duodenal biopsy. Interestingly, at the first 
presentation, the morphology was normal but TG2 deposits were present as in the renal biopsy. 
After one year, a new biopsy of intestine was performed showing this time morphological 
changes and abnorm alities.  
 
Major points:  
- This case report is very interesting, but do not support the conclusion. This is not the first 
case report with patient suffering with IgAN and a gluten involvement. Several case reports 
showed that a gluten diet ameliorates the r enal symptoms (Koivuviita N et al 2009 NDT, La 
Villa G et al 2003 W J Gastroenterol, Woodrow G et al 1993 NDT) and two studies, one is 
cited in this article (Coppo et al 1990 Clin Nephrol, Yagame M et al 1988 nephron) 
described the changes in gluten diet a nd their influence on IgAN patients. Moreover, in this 
case report, it is only an association between TG2 presence in the intestine and IgAN, so 
gluten could participate or not. What happens after the gluten diet? The major effect on 
IgAN is due to steroid s in this case report. The title and the conclusion are overstated and 
should be reformulated.  
 
- The authors did not discuss the association between cystic fibrosis and celiac disease.  
 
- "Monteiro et al showed as activation of TG2 is crucial for the depos ition of immune -
complexes" ref 12 is wrong. The pathological role of TG2 in IgAN was shown in Berthelot 
et al J Exp Med 2012. Lechner et al JASN 2016 showed that the removal of IgA deposits 
leaded to the decrease of TG2 staining.  
 
- The role of gluten in a nimal models of IgAN was also shown in Papista et al Kidney Int 
2015 and not only in the article Coppo et al JASN 1992.   
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 requ ire 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 or 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 re lating 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 intere sts? 
 
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 at tachments 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