PONE-D-20-27317

Interleukin-18 and Interferon-γ Single Nucleotide Polymorphisms in Egyptian patients with Tuberculosis.

PLOS ONE

Dear Dr. Hassuna,

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PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. 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

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: No

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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: Yes

Reviewer #2: Yes

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

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Reviewer #1: No

Reviewer #2: 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 work deals with an essential subject of infectious diseases, including tuberculosis.

However, it needs to be revised again:

1. the linguistic correctness and clarity of the document should be checked

2. the text should be stylistically uniform and adapted to the requirements of the journal

2. it is necessary to harmonize the writing of genes with or without information on pairs of alleles

3. in the text, spaces separating numerical values from units are missing several times

4. the storage temperature of the samples should be verified

5. in the description of the results, double brackets appear several times, with no justification

6. in Table 1, the number of decimal places should be standardized

7. discussion should be enriched with additional publications analyzing SNP polymorphism in tuberculosis

Reviewer #2: - Studies on the role of genetics in the pathogenesis of susceptibility to TB disease is always interesting. In this study, authors objective is to find whether there in an association between SNP-607 C/A and -137 G/C in IL-18 gene and also SNP +874 A/T IFN-gamma gene with susceptibility to TB both pulmonary and extrapulmonary in the Egyptian population. There is no clarity regarding this matter yet. Various studies and meta-analyzes with populations from different countries, races and ethnicities show inconclusive results, although most of the results show no association. This study is quite interesting because it is the first study conducted in Egyptian and the results show that there is an association at least between SNP -137 G / C of IL-18 gene and susceptibility to suffer from TB. I have a few questions and comments as follows:

- Abstract section

o To emphasize the importance of this study, it will be better if a background subheading added in the abstract

o In methods section the study design must be mention

o There are inconsistency in conclusion, authors was not mention association between SNP in IFN gamma and TB susceptibility, while it was appear in objective and result, meanwhile authors draw a conclusion on possible association these SNPs and the development of drug resistance which was not appear in objective section and also was not back up by data in abstract results section

- Methods section

o How authors define cases? How do they diagnose pulmonary and extra pulmonary TB?

o How about inclusion criteria? is it only new TB cases or previously treated TB cases also enrolled in the study?

o How the authors define control? It was not written in the manuscript

o Authors also should explain on how matching process was done or was not done

- Results section

o Table 1 only showed basic characteristic of cases but not controls. The data is important to show the homogeneity between cases and controls. It might be possible that the difference in basic characteristics such as comorbidities between groups that increasing the susceptibility to TB

o The OR in table 2, is it adjusted or crude OR?

o Page 12 last paragraph. How drug resistance determined? Authors should also notify this in the method section

- There were several typos on write SNP, please make appropriate correction

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Reviewer #1: No

Reviewer #2: No

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Interleukin-18 and Interferon-γ Single Nucleotide Polymorphisms in Egyptian patients with Tuberculosis.

PONE-D-20-27317R1

Dear Dr. Hassuna,

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,

Cinzia Ciccacci

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 #2: 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 #2: (No Response)

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

Reviewer #2: (No Response)

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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 #2: (No Response)

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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 #2: (No Response)

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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 #2: (No Response)

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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 #2: No