Clinical significance of non-thyroidal illness syndrome on disease activity and dyslipidemia in patients with SLE

Xin Zhang; Lirong Liu; Xiaolei Ma; Wei Hu; Xue Xu; Saisai Huang; Bingzhu Hua; Hong Wang; Zhiyong Chen; Lingyun Sun

doi:10.1371/journal.pone.0231622

Peer Review History

Original SubmissionDecember 22, 2019
2 Mar 2020 Decision Letter - Deyu Fang, Editor PONE-D-19-35454 Clinical significance of non-thyroidal illness syndrome on disease activity and dyslipidemia in patients with SLE PLOS ONE Dear Dr. Chen, 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. As what recognized by the reviewer, the observation that a correlation of the low FT3 with SLE disease activity in a Chinese population provide some useful insights for a better understudying the disease pathogenesis. However, important analysis of these correlations in patients with NTIS and in patients without NTIS separately is missing, which is critical to understand whether the association of low FT3 with SLE is associated to NTIS pathogenesis . Please carefully address all reviewer's concerns and the editor will be happy to consider its possible publication. We would appreciate receiving your revised manuscript by March 30th. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. 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We look forward to receiving your revised manuscript. Kind regards, Deyu Fang, Ph.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 http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf [Note: HTML markup is below. Please do not edit.] 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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 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 ****** 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 ****** 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 performed Pearson's regression model as well as univariate and multivariate logistic regression analyses, and provided correlations between FT3 and UP, GBG, EST, BUN, SLEDAI, Cr, as well as CRP. Thus, they concluded that low FT3 is assosiated with disease activity and an independent risk factor for dyslipidemia in patients with SLE. This article was presented in an intelligible fashion and written in standard English. ****** 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 [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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: comments.docx https://doi.org/10.1371/journal.pone.0231622.r001
Revision 1
13 Mar 2020 Author Response Comments from the editor: 1.This study “Clinical significance of non-thyroidal illness syndrome on disease activity and dyslipidemia in patients with SLE” validated the association between FT3 and SLE disease. They discovered that a low FT3 is associated with SLE disease activity, and a low FT3 is an independent risk factor for dyslipidemia in patients with SLE. This study, while confirmative, provided useful information for FT3 in Chinese population. Despite the authors identified FT3 is a risk factor for dyslipidemia in SLE patients, they didn’t provide the direct correlation analysis between TF3 and biomarkers of lipid profiles. Reply: Thank you for you critical comments, we revised our manuscript according your advice (see below). Comments from the reviewers: 1.The authors found that FT3 levels in serum are negatively correlated with the levels of UP, FBG, ESR, BUN, SLEDAI, Cr, as well as CPR. However, the correlations are weak, as shown by the values of correlation coefficients (r) in figure 1. Moreover, it’s unknown how NTIS pathogenesis contributes to these correlations. Therefore, analyzing these correlations in patients with NTIS and in patients without NTIS separately may better address this question. Reply: Thank you for you critical comments. We analyzed the associations in patients with NTIS and in patients without NTIS separately. The results showed that the FT3 levels were negatively correlated with 24 h UP (r = -0.301; p < 0.001; Fig. 1A), BUN (r = -0.325; p < 0.001; Fig. 1B), Cr (r = -0.298; p < 0.001; Fig. 1C), as well as SLEDAI (r = -0.313; p < 0.001; Fig. 1F). However, these correlations were not observed in patients without NTIS (Fig. 2A, 2B, 2C and 2F). In addition, FT3 were negatively correlated with CRP in both NTIS patient (r = -0.200; p < 0.05; Fig. 1D) and euthyroid patients (r = -0.254; p < 0.05; Fig. 2D), ESR (r = -0.27; p < 0.05; Fig. 2E) in NTIS patients rather than in euthyroid patients (Fig. 1E). These results indicate that low levels of FT3 are closely related to a higher SLE disease activity mainly in NTIS patients rather than in euthyroid patients. SLE is a heterogeneous disease and the aetiology is very complicated. The weak but statistically significant correlations found in this study suggests that NTIS maybe one of the factors impacting the disease activity and long-term prognosis of SLE. 2.The above concern applies also to relationships between the ApoB/ApoA1 and CRP, ESR, Cr, UP, as well as SLEDAI in figure2. Reply: We analyzed the associations in patients with NTIS and in patients without NTIS separately. We found that the ApoB/ApoA1 ratio was significantly associated with SLEDAI (r = 0.251; p < 0.01; Fig.3E) but not with CRP, ESR, Cr, or 24 h UP (Fig. 3A, 3B, 3C and 3D) in NTIS patients. In euthyroid patients, the ApoB/ApoA1 ratio was significantly associated with CRP (r = 0.428; p < 0.001; Fig 4A) and ESR (r = 0.315; p < 0.01; Fig. 4B), but not with Cr, 24 h UP and SLEDAI (Fig. 4C, 4D and 4F). These results indicate that the atherogenic ApoB/ApoA1 ratio are somewhat related to the SLE disease activity in NTIS patients, as well as immunologic inflammation in euthyroid patients. 3.The resolution for Figure1 and Figure2 could be improved. Reply: We increased the figure resolution to 300 × 300 dpi. 4.The actual number of recruited patients is 223. However, it’s inconsistent in the article. Reply：Thank you for your careful review, we corrected this error. In addition, we deleted the data about fasting blood glucose, because it is neither a criteria of dyslipidemia nor a criteria for SLEDAI. Attachments Attachment Submitted filename: comments-Pone.docx https://doi.org/10.1371/journal.pone.0231622.r002
30 Mar 2020 Decision Letter - Deyu Fang, Editor Clinical significance of non-thyroidal illness syndrome on disease activity and dyslipidemia in patients with SLE PONE-D-19-35454R1 Dear Dr. Chen, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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. With kind regards, Deyu Fang, Ph.D. 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 ******** 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: The authors fully addressed my concerns, and the added new data support their conclusions. The statistical analysis has been performed appropriately. ****** 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 https://doi.org/10.1371/journal.pone.0231622.r003
Formally Accepted
2 Apr 2020 Acceptance Letter - Deyu Fang, Editor PONE-D-19-35454R1 Clinical significance of non-thyroidal illness syndrome on disease activity and dyslipidemia in patients with SLE Dear Dr. Chen: I am 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 notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Deyu Fang Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0231622.r004

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