PONE-D-23-37483Correlation analysis of serum TLR4 protein levels and TLR4 gene  polymorphisms in gouty arthritis patientsPLOS ONE

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Natural Science Foundation of Xinjiang(2022D01C756,2020D01C263), Special fund project of youth scientific Research sailing from The First Affiliated Hospital of Xinjiang Medical University (2022-74), 

Natural Science Foundation of China (81460153, 82002276).

  

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Additional Editor Comments:

Dear Dr. Lei Miao,

After careful consideration and consultation of the comments provided by the reviewers, there are several issues which would need to be addressed for your submitted material to become acceptable for publication by PLOS ONE. The main issues are outlined by the first reviewer and are mostly related to the lack of information related to TLR functions related to gout, and perhaps more importantly, the choice of statistical tools selected for the analysis of the results.

The discussion section would require addressing a more general conclusion, expanding outside of the scope of the tested sub-population.

If you decide to submit a revised version of the manuscript, please make sure that you address or answer all the various comments outlined by the reviewers.

Sincerely,

Philippe T. Georgel, PhD

Academic Editor for 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: Partly

Reviewer #2: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: 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: Yes

Reviewer #2: Yes

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4. 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

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: In this paper, Liu et al set out to identify possible correlations between TLR4 polymorphisms and plasma concentration and gouty arthritis. They did so by recruiting a 1207 study partipants. Even though their conclusions do appear sound, the work has some limitations that require improvement.

1-Overall this manuscript is very sparse on properly referring to previous work. This is most notorious in the introduction section. References ought to be added to the following sentences:

a) TLR expression by immune cells have been throuroughly described by multiple research papers and review articles. In this way, the sentence “TLR is the upstream signal of NF-κB in the TLR inflammatory pathway, which is an important pattern recognition receptor in the immune system, and it is present in various immune cells (T cells, B cells, and natural killer cells) as well as in monocytes, macrophages, neutrophils, and epithelial cells.” Ought to contain at least a reference to a review article such as, Fitzgerald KA, Cell 2020

b) Multiple papers have linked TLRs, and particularly TLR4, to immunological diseases in humans. Thus, the sentence “TLR-related genes have been linked to immunological illnesses, but little is known about their etiology and the factors that influence gout.” ought to be complemented by the following references:

- Reynolds, J. M Proc. Natl Acad. Sci. 2012.

-Amaral-Silva, D. Commun. Biol. 2021

- Ospelt, C. Arthritis Rheum. 2008

c) Even more pertinently to the work being presented in this manuscript, it misses the references where urate crystals have been identified as TLRs ligands in the sentence “For example, in patients with gouty arthritis, the release of urate crystals from damaged cells is an endogenous danger signal, thus indicating a link between gout pathogenesis and TLRs.”

2-Figure/Table legends ought to specify the number of study participants for each group that were sampled.

3- Similarly, the statistical tests used for each figure and table must be specified in figure/table legends

4-In the discussion section it is not clear what the authors mean by “non-specific immune cells” This denomination should be either clarified or removed from the text.

Reviewer #2: 1. What were the specific requirements for the quality and concentration of sample DNA in this study?

2. What was the basis for selecting rs2149356, rs2737191and rs10759932 loci of TLR4 gene in this study?

3. All data in Table 1 could be directly viewed in the database without any information added in this study. Was a separate list appropriate?

4. Please added the manufacturers and product numbers of the main kits in this study.

5. Why were the genotyping results not validated by sampling sequencing?

6. Why did the author not choose a two-tailed test during statistical analysis?

7. Table 3, 4 and 5 were the basic characteristics of the research objects, and it was suggested to combine the three tables.

8. Did the three loci of the TLR4 gene in this study conform to Hardy-Weinberg equilibrium?

9. The research object of this article is limited to a population in one region, and the conclusion does not emphasize whether the specific population is appropriate?

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Reviewer #1: No

Reviewer #2: No

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Correlation analysis of serum TLR4 protein levels and TLR4 gene  polymorphisms in gouty arthritis patients

PONE-D-23-37483R1

Dear Dr. Lei Miao,

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,

Philippe T. Georgel

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

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 #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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 #1: Yes

Reviewer #2: Yes

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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 #1: Yes

Reviewer #2: Yes

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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 #1: All my initial revision requests were satisfactorily addressed. At this time I have no more comments to make

Reviewer #2: The author has made appropriate changes, additions or explanations based on the reviewer's comments. It is recommended to receive.

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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

Reviewer #2: No

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