Peer Review History

Original SubmissionJanuary 26, 2021
Decision Letter - Manal S. Fawzy, Editor

PONE-D-21-02804

Clinical relevance for circulating cold inducible RNA-binding protein (CIRP) in patients with adult-onset Still’s disease

PLOS ONE

Dear Dr. Fujita,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by May 27 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Manal S. Fawzy, Ph.D., M.D.

Academic Editor

PLOS ONE

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified:

 - whether consent was obtained

 - whether consent was informed

 - what type of consent you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed).

 - if your study included minors, state whether you obtained consent from parents or guardians.

 - if the need for consent was waived by the ethics committee, please include this information.

3. In your Methods section, please provide additional information about the participant recruitment method and the demographic details of your participants. Please ensure you have provided sufficient details to replicate the analyses such as:

a) a statement as to whether your sample can be considered representative of a larger population, and

b) a description of how participants from each group were recruited.

4. Thank you for providing the date(s) when patient medical information was initially recorded. Please also include the date(s) on which your research team accessed the databases/records to obtain the retrospective data used in your study.

5. Please provide the catalog numbers of the ELISA kits used in the study.

6. Thank you for stating the following in the Competing Interests section:

"Kiyoshi Migita has received research grants from Chugai, Pfizer, and AbbVie. Rest of the authors declares that they have no competing interests."

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to  PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests

7. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works.

- https://doi.org/10.1186/s13075-020-02263-3

- https://doi.org/10.1002/JLB.3MIR1118-443R

We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable, even for works which you authored. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications.

Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work.

We will carefully review your manuscript upon resubmission, so please ensure that your revision is thorough.

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

**********

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

Reviewer #1: Yes

Reviewer #2: No

**********

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

**********

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: No

**********

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: 1. The age of the control, AOSD and RA groups were significantly different, which may affect immune response.

2. In the method section, please explain the drawing time of the laboratory data as well as the drawing time for CIRP before and after treatment.

3. Please add IL-18 in table 1

4. Fig 1 please confirm the number of patients in each group

5. Some writing error: such as: figures, ASD should be AOSD

Reviewer #2: This article explored the clinical significance of serum CIRP levels in AOSD for the first time. According to the article, the serum CIRP levels seem to significantly be elevated in AOSD patients and be related to the disease activity of AOSD.

Strengths:

CIRP was a ligand to TREM-1 and the interaction of them could aggravate inflammatory responses, thus, the elevated serum CIRP may related to the pathogenesis of AOSD.

Weaknesses:

1. The sample size of this study is relatively small.

2. They only included RA as disease control, but the differential diagnosis of AOSD should be made among infectious diseases, hematological malignancy etc.

**********

6. 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

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 1

Response to Reviewer #1

We wish to express our appreciation to your insightful comments on our paper. The comments have helped us significantly improve the paper.

Comment

1. The age of the control, AOSD and RA groups were significantly different, which may affect immune response.

Response

I appreciate for your critical comment. The association between CIRP and age has not been reported. I added systemic lupus erythematosus (SLE) patients as control. The age between AOSD and SLE were equal and serum levels of CIRP in AOSD patients were significantly higher than that in SLE patients. Therefore, I consider the age did not affect immune response.

Comment

2. In the method section, please explain the drawing time of the laboratory data as well as the drawing time for CIRP before and after treatment.

Response

I appreciate for important your comment. In accordance with your comment, I added as follows; “A total of 44 untreated AOSD patients and 15 healthy controls (HCs) were included in the training and validation sets.” “We additionally collected serum samples from 8 treated AOSD patients at the time of remission in order to explore the longitudinal changes.”

Comment

3. Please add IL-18 in table 1

Response

I appreciate for important your comment. In accordance with your comment, I added IL-18 in table 1.

Comment

4. Fig 1 please confirm the number of patients in each group

Response

I appreciate for your comment. I remake correctly figure 1 because of the number of patients was wrong.

Comment

5. Some writing error: such as: figures, ASD should be AOSD

Response

I appreciate for your important comment. I unified the abbreviation of adult onset Still’s disease to AOSD in this manuscript.

Response to Reviewer 2

We wish to express our appreciation to your insightful comments on our paper. The comments have helped us significantly improve the paper.

Comment

This article explored the clinical significance of serum CIRP levels in AOSD for the first time. According to the article, the serum CIRP levels seem to significantly be elevated in AOSD patients and be related to the disease activity of AOSD.

Strengths:

CIRP was a ligand to TREM-1 and the interaction of them could aggravate inflammatory responses, thus, the elevated serum CIRP may related to the pathogenesis of AOSD.

Weaknesses:

1. The sample size of this study is relatively small.

Response

I appreciate for your critical comment. Since AOSD was rare disease, the sample size of this study was relatively small. I added two newly diagnosed patients. Therefore, the number of patients was increased from 42 to 44.

Comment

2. They only included RA as disease control, but the differential diagnosis of AOSD should be made among infectious diseases, hematological malignancy etc.

Response

I appreciate for your critical comment. As you pointed out, it is important to compare the multiple diseases since the differential diagnosis of AOSD is diverse. I could not collect enough number of infectious diseases and hematological malignancy patients. However, I added systemic lupus erythematosus patients as control. Since AOSD and SLE cause hemophagocytic syndrome, the different diagnosis between AOSD and SLE is especially important. This additional study revealed that serum levels of CIRP in AOSD patients were significantly higher than that in SLE patients. Therefore, I added as follows; “As shown in Fig 1, serum levels of CIRP were significantly higher in patients with AOSD (median: 9.6 ng/mL, IQR [6.1–13.7]) compared to those in patients with RA (3.2 ng/mL, IQR [1.9–3.8]; p < 0.001), SLE (2.2 ng/mL, IQR [1.9–2.4]; p < 0.001) and in HCs (2.8 ng/mL, [IQR; 1.4–4.9], p < 0.001).”

Editor Comments

Comment

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Response

I appreciate for your important comment. I ensured our manuscript meets PLOS ONE's style requirements, and revised manuscript exactly.

Comment

2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified:

- whether consent was obtained

- whether consent was informed

- what type of consent you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed).

- if your study included minors, state whether you obtained consent from parents or guardians.

- if the need for consent was waived by the ethics committee, please include this information.

Response

I appreciate for your critical comment. In accordance with your comment, I added details regarding participant consent as follows in methods section; “The study was conducted with the approval of the Ethics Committee of Fukushima Medical University (No. 2889). As this was a retrospective study, the need for written informed consent was waived.”

Comment

3. In your Methods section, please provide additional information about the participant recruitment method and the demographic details of your participants. Please ensure you have provided sufficient details to replicate the analyses such as:

a) a statement as to whether your sample can be considered representative of a larger population, and

b) a description of how participants from each group were recruited.

Response

I appreciate for you essential comment. Patients from wide range of Fukushima prefecture were recruited. Therefore, I think our sample can be considered representative of larger population.

I added the description how to recruit the patients in methods section as follows; “All patients diagnosed with AOSD at the Department of Rheumatology, Fukushima Medical University Hospital from January 2005 to April 2020 were enrolled. All records were accessed from January 2020 to October 2020.”

“HCs lacked chronic medical diseases or conditions and did not take prescription medications or over-the-counter medications within seven days.”

“Patients diagnosed with RA and SLE in Fukushima Medical University Hospital were randomly selected.”

Comment

4. Thank you for providing the date(s) when patient medical information was initially recorded. Please also include the date(s) on which your research team accessed the databases/records to obtain the retrospective data used in your study.

Response

I appreciate for your important comment. In accordance with your comment, we added as follows in methods section” All patients diagnosed with AOSD at Department of Rheumatology, Fukushima Medical University Hospital from January 2005 to April 2020 were enrolled. All records were accessed from January 2020 to October 2020.”

Comment

5. Please provide the catalog numbers of the ELISA kits used in the study.

Response

I appreciate for your comment. I added the catalog numbers of the ELISA kits as followed in method section; “Serum concentrations of CIRP� were measured using enzyme-linked immunosorbent assay (ELISA) kits (MBL, Nagoya, Japan; Code No, CY-8103) according to the manufacturer's instruction. Similarly, Serum IL-18 was measured by ELISA Kits (MBL, Nagoya, Japan; Code No. 7620).”

Comment

6. Thank you for stating the following in the Competing Interests section:

"Kiyoshi Migita has received research grants from Chugai, Pfizer, and AbbVie. Rest of the authors declares that they have no competing interests."

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests

Response

I appreciate for your important comment. I confirmed this does not alter our adherence to PLOS ONE policies on sharing data and materials. Therefore I included our updated Competing Interests statement in our cover letter as follews;” Kiyoshi Migita has received research grants from Chugai, Pfizer, and AbbVie. Rest of the authors declares that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.”

Comment

7. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works.

- https://doi.org/10.1186/s13075-020-02263-3

- https://doi.org/10.1002/JLB.3MIR1118-443R

We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable, even for works which you authored. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications.

Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work.

We will carefully review your manuscript upon resubmission, so please ensure that your revision is thorough.

Response

I appreciate for your critical comment. I confirmed previous publish works pointed out by editors, and I rephrase the duplicated text.

Decision Letter - Manal S. Fawzy, Editor

PONE-D-21-02804R1

Clinical relevance for circulating cold-inducible RNA-binding protein (CIRP) in patients with adult-onset Still’s disease

PLOS ONE

Dear Dr. Fujita,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Aug 21 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Manal S. Fawzy, Ph.D., M.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

Please address the raised concern by the reviewer and highlight in the revised version of the manuscript.

[Note: HTML markup is below. Please do not edit.]

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

**********

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: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: No

**********

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

**********

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

**********

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: The authors answered all questions well. In my opinion, I do not think I can give some suggestions for current version.

Reviewer #2: The authors added SLE and RA as disease control, but the medication seems diverse in RA patients (the medication of SLE patients not described). The influence of medication such as glucocorticoids may also affect the level of CIRP.

**********

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

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 2

Response to Reviewer #1

Comment

The authors answered all questions well. In my opinion, I do not think I can give some suggestions for current version.

Response

I am grateful for your comment

Response to Reviewer 2

We wish to express our appreciation to your insightful comments on our paper. The comments have helped us significantly improve the paper.

Comment

The authors added SLE and RA as disease control, but the medication seems diverse in RA patients (the medication ofSLE patients not described). The influence of medication such as glucocorticoids may also affect the level of CIRP.

Response

I appreciate for your critical comment. All SLE patients was untreated. Among 50 RA patients, 8 RA patients was untreated. We added the comparison between untreated AOSD and untreated RA as follows, “Serum levels of AOSD patients were significantly higher than that of untreated RA (2.6 ng/mL, [IQR; 1.7-3.8], p<0.001).”

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Manal S. Fawzy, Editor

Clinical relevance for circulating cold-inducible RNA-binding protein (CIRP) in patients with adult-onset Still’s disease

PONE-D-21-02804R2

Dear Dr. Fujita,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Manal S. Fawzy, Ph.D., M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have adequately addressed the concerns raised by the reviewers.

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

**********

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: Yes

**********

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

Reviewer #2: 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 #2: 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 #2: 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 #2: The authors clarified my concerns well. From my point of view, I have no more questions or suggestions.

**********

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

Formally Accepted
Acceptance Letter - Manal S. Fawzy, Editor

PONE-D-21-02804R2

Clinical relevance for circulating cold-inducible RNA-binding protein (CIRP) in patients with adult-onset Still’s disease

Dear Dr. Fujita:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Professor Manal S. Fawzy

Academic Editor

PLOS ONE

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .