The Evolution of Our Understanding of Immunoproliferative Small Intestinal Disease (IPSID) over Time

Round 1

Reviewer 1 Report

1. Line 84 suggest change the term "malignant lymphoma" to "aggressive lymphoma"
2. Please review the sequence of references , later reference are mentioned earlier in the manuscript : example line 106 - reference 20 is out of sequence - the authors should have spent some time on organizing the reference list - The authors need to carefully review the listing of the references
3. line 258 , other markers expressed , listing these may confuse some readers, either remove the whole sentence or explain why CD3 a T cell markers was expressed on a B cell lymphoplasmacytic disorder and more why IgG or IgM are expressed on an usually IgA IPSID
4. Review the manuscript carefully for minor english spelling errors example line 225 = lymphoplasmacytes  

Author Response

We highly appreciate the time and effort you put in providing your valuable feedback and insightful comments. We have been able to incorporate changes to reflect most of the suggestions provided

Comment 1: Line 84 suggest change the term "malignant lymphoma" to "aggressive lymphoma"

Response: We agree with this comment and we have changed it in the revised manuscript

Comment 2: Please review the sequence of references , later reference are mentioned earlier in the manuscript : example line 106 - reference 20 is out of sequence - the authors should have spent some time on organizing the reference list - The authors need to carefully review the listing of the references

Response: We thank you for pointing it out and we have revised the sequence of reference as advised

Comment 3: line 258 , other markers expressed , listing these may confuse some readers, either remove the whole sentence or explain why CD3 a T cell markers was expressed on a B cell lymphoplasmacytic disorder and more why IgG or IgM are expressed on an usually IgA IPSID

Response: We agree that it might be confusing for the readers, so we removed this part as suggested

Comment 4: Review the manuscript carefully for minor english spelling errors example line 225 = lymphoplasmacytes 

Response: We agree, accordingly, we have corrected the spelling errors. 

Thanks again for your kind review 

 

Reviewer 2 Report

Very interesting and comprehensive review of this rare entity. Nothing to add.

Author Response

We highly appreciate the time and effort that you have dedicated in reviewing our manuscript and for your valuable and kind feedback

Reviewer 3 Report

In this review by  AlYamany et al., the authors the evolution of the immunoproliferative small intestinal disease (IPSID) with special emphasis on the epidemiology, diagnosis and management options of the disease. This topic is of great interest due to the scarce literature reports on this disease.  However, this review has to be improved in order to add up more knowledge on IPSID with respect to other published papers. Here are some suggestions.

Major comments:

1. Title: avoid abbreviation of IPSID; write the complete definition.
2. The abstract needs to explain the background of the problem to be addressed, the state of the art, the aim of the review etc. Please include a longer abstract with the issues considered in this paper.
3. Introduction: give an update on the current worldwide situation, clinical features of the disease, introduce the problem with the studies on this disease.
4. In the section 3: Etiology and Pathophysiology, for instance, provide a short description of small intestine barrier. How is it altered in this disease? Any link between IPSID and dysbiosis? The following studies may be of help: PMID 33267569; 34589512; 34886561
5. Sections 8.1, 8.3 to 8.5 are important, and should be further discussed. Please expand these sections.
6. Figure 3: add more details about the antibiotics used in each stage.
7. Discuss the aspects considered with a new point of view with respect to published reviews on IPSID, providing ways to improve diagnosis, treatment etc.

Minor comments:

1. Legends of Figures 2 and 3 should be expanded.
2. Check typos throughout the text: e.g., line 343: “is not knows” should read is not known.

Author Response

Thank you for your kind review. We highly appreciate the time and effort you have dedicated to providing your insightful comments and valuable feedback on our manuscript. 

We have been able to incorporate some changes according to the comments of the reviewer as follows:

Comment 1: Title: avoid abbreviation of IPSID; write the complete definition.

Response: We have fixed the abbreviation of IPSID in the title and made sure to mention the full name and abbreviation in the introduction in order for it to be evident throughout the paper. 

Comment 2: The abstract needs to explain the background of the problem to be addressed, the state of the art, the aim of the review etc. Please include a longer abstract with the issues considered in this paper.

Response: Thank you for pointing this out. We agree with this comment. Therefore, we have expanded the abstract to include the aim of the review and the background of the problem.

Comment 3: Introduction: give an update on the current worldwide situation, clinical features of the disease, introduce the problem with the studies on this disease.

Response: Thank you for this suggestion. However, we have given detailed information on each suggested aspect after the introduction in separated sections. 

Comment 4: In the section 3: Etiology and Pathophysiology, for instance, provide a short description of small intestine barrier. How is it altered in this disease? Any link between IPSID and dysbiosis? The following studies may be of help: PMID 33267569; 34589512; 34886561

Response: Thank you for this valuable input, and we agree with this recommendation. We have added a paragraph on the intestinal barrier and briefly on the alterations in the intestinal barrier that happen with inflammatory diseases of the intestine. Special thanks for the suggested articles. 

Comment 5: Sections 8.1, 8.3 to 8.5 are important, and should be further discussed. Please expand these sections.

Response: We agree with this recommendation; however, unfortunately, due to the paucity of the disease and reports on it, there is not enough available data on these aspects of treatment for IPSID. We added in our conclusion section to further investigate these therapeutic options in IPSID as areas for future research.

Comment 6: Figure 3: add more details about the antibiotics used in each stage

Response: We agree with this comment, and we have incorporated it into the manuscript

Comment 7: Discuss the aspects considered with a new point of view with respect to published reviews on IPSID, providing ways to improve diagnosis, treatment etc.

Response: Within the description of each section, we have tried to implement the latest published information on each aspect of the disease and therapies. 

Minor Comments: Typos have been fixed, and expansion of the legends as allowed in the manuscript was adjusted

Thank you for your valuable input and kind review 

Round 2

Reviewer 3 Report

The authors have revised according to this reviewer's suggestions