A Potential Role of Interleukin-5 in the Pathogenesis and Progression of Amyotrophic Lateral Sclerosis: A New Molecular Perspective

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

review report attched

Comments for author File: Comments.pdf

Comments on the Quality of English Language

suggested in review report

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript addresses an important and current issue about the role of immune regulation in ALS.  I have concerns about the number of weak correlations presented.  Several other papers have not yet found the significance of the circulating pro- and anti- inflammatory cytokines.  Therefore, it would be important to make sure that there are stronger correlations between the cytokine profiles and ALS parameters.

Comments:

1.       In the results, the demographic and clinical data was nicely presented.  The Figure 1 was nicely presented and interesting.

2.      The correlation analysis had many low r values suggesting many weak correlations (<0.3) to moderate correlations (0.5-0.3) but no strong correlations.  The best positive correlation appeared to be ALSFRS-R and IL-5.  The ALSFR-RUL, ALSFR-R-R, and ΔPR and IL5 all have weak correlations. Similar with several other cytokine correlations.  Therefore, I am not sure there is strength in the association of IL-5 with ALSFR-R subscores or progression rate.  Could the authors comment on this.

3.      The last section of correlations between smoking, ETOH, and BMI also have weak correlations and could probably be omitted.

4.  The discussion is very long and hard to follow.  A more concise discussion surrounding the main positive findings of the paper would be more readable.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Article can be accepted for publication.

Author Response

We are grateful for your appreciation.

Reviewer 2 Report

Comments and Suggestions for Authors

Rereview:

1.      2.  The correlation analysis had many low r values suggesting many weak correlations (<0.3) to moderate correlations (0.5-0.3) but no strong correlations.  The best positive correlation appeared to be ALSFRS-R and IL-5.  The ALSFR-RUL, ALSFR-R-R, and ΔPR and IL5 all have weak correlations. Similar with several other cytokine correlations.  Therefore, I am not sure there is strength in the association of IL-5 with ALSFR-R subscores or progression rate.  Could the authors comment on this.

Reviewer’s follow-up comment:  The results should make some comment about the strength of the correlations. Authors could consider removing some of the very weak correlations with near flat-line graphs.  Appreciate that the limitation of the study was added and included a statement about the weak correlations.

2.       The discussion could do with shortening by a few paragraphs, concentrating on the relevance of the findings. 

Comments on the Quality of English Language

There are minor typographical errors but overall English language is not a problem.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

No new comments.