PONE-D-21-18558

Serum levels of NLRC4 and MCP-2/CCL8 in patients with active Crohn’s disease

PLOS ONE

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PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

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Reviewer #1: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors studied – for the first time - the serum levels of MCP2/CCL8 and NLRC4 in active CD and found significant differences compared with the control group. This finding could be useful in clinical practice, both in diagnostic and therapy of CD.

I have some suggestions for the authors:

1. The Montreal classification of CD (location, behavior) – has no relevance in this study.

2. Please be more precious regarding the selection of the control group; as there are significant differences regarding age and sex it would be useful to check if there are any variation of studied inflammatory markers in general population related to age and sex.

3. There are some already known inflammatory markers (CRP, RDW, WBC, neutrophils, NLR, PLR, platelets) found to be different from control group but this is not relevant in this study; it would be interesting to compare these known markers with MCP2/CCL8 and NLRC4.

4. It is well known that it is no correlation between CDAI and mucosal inflammation; maybe adding calprotectin evaluation will add additional value of the study.

5. Some items in the discussion section are not supported by the results (“This supports the role of neutrophils in regulating leukocyte activation and migration in the intestinal damage, inflammation in general, and also as an indicator of disease severity”).

6. The treatment may play a role in levels of MCP2/CCL8 and NLRC4. Although the patients had active CD only 31 had treatment. Please explain.

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Reviewer #1: No

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Serum levels of NLRC4 and MCP-2/CCL8 in patients with active Crohn’s disease

PONE-D-21-18558R1

Dear Dr. Irak,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

David M. Ojcius

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: It is an interesting work that evaluates, for the first time, the role of serum levels of MCP2/CCL8 and NLRC4 in active CD.

The authors responded promptly to all comments in the first revision.

Although some problems remain insufficiently evaluated (value of markers used in inactive CD compared to the control group, correlation with endoscopic activity / fecal calprotectin) I believe that, through the quality of the study and the novelty of the approach, the paper can be published.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No