Evaluation of usefulness in surfactant protein D as a predictor of mortality in myositis-associated interstitial lung disease

Shinjiro Kaieda; Takahisa Gono; Kenichi Masui; Naoshi Nishina; Shinji Sato; Masataka Kuwana; A Multicenter Retrospective Cohort of Japanese Patients with Myositis-associated ILD (JAMI) investigators

doi:10.1371/journal.pone.0234523

Peer Review History

Original SubmissionMarch 18, 2020
21 Apr 2020 Decision Letter - Minghua Wu, Editor PONE-D-20-07783 Evaluation of usefulness in surfactant protein D as a predictor of mortality in myositis-associated interstitial lung disease PLOS ONE Dear Dr. Gono, 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. We would appreciate receiving your revised manuscript by Jun 05 2020 11:59PM. 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. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols 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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Minghua Wu, M.D., 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 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. Thank you for including the following consent information on the submission details page: 'Consent was not obtained because the data were analyzed anonymously.' Please also include this information in the ethics statement in the Methods section of your manuscript. 3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. 4. We note that you have a patent relating to material pertinent to this article. a. Please provide an amended statement of Competing Interests to declare this patent (with details including name and number), along with any other relevant declarations relating to employment, consultancy, patents, products in development or modified products etc. Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” 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. b. This information should be included 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 5. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ [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 Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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 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: 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: Comments for Authors Kaieda S et al. examined the utility of SP-D as a predictive biomarker for mortality in patients with ILD associated with PM/DM using JAMI cohort. Overall the manuscript is on important topic and is well written and analyzed with clarity and conviction. I have an only minor concern which authors need to answer. Minor 1. I agree with authors lower SP-D levels is potentially relevant to the rapid progressive course of anti-MDA5 antibody-associated ILD and the level could be low at the disease diagnosis. However, is there any speculation on the issue which patients with anti-ARS had a higher level of SP-D among other MSAs? Since the elevated serum levels of SP-D could be attributed to an increase in SP-D production by regenerating alveolar type II pneumocytes, did the patients with anti-ARS have already widespread findings of ILD on chest CT at diagnosis or have longer disease duration from diagnosis of ILD? Reviewer #2: Kaieda S, et al. investigated serum SP-D as a predictive biomarker for mortality in patients with PM/DM-associated ILDs. They also performed stratified analysis by anti-MDA5, anti-ARS, or double-negative and identified a cut-off value at 127.6 ng/ml for their mortality in double-negative group. Indeed, SP-D was not significantly predictive in patients with anti-MDA5 and anti-ARS. This is nicely designed and well performed clinical study that inform usefulness of serum SP-D in PM/DM-associated ILDs. However, several points to strengthen then manuscript were as below: #1 Please provide intra-class comparison of non-survivor vs. survivor in each MSA group. #2 It should be emphasized that serum SP-D is approved as a laboratory test for clinical use and easily available at clinical practice in Japan, however it is approved only for research use in many countries other than Japan including Europe and North America. Also, it should be pronounced that serum SP-D might be beneficial for patients outside Japan if the test were approved for clinical use. #3 Please enrich discussion about reasons for the difference in serum SP-D levels by MSA. Especially, focusing on mechanisms of translocation of SP-D molecules from alveolar epithelium to serum and on difference in damage of peripheral pulmonary structure by MSAs would be preferable. ****** 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 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. https://doi.org/10.1371/journal.pone.0234523.r001
Revision 1
15 May 2020 Author Response Dear Editor and Reviewers Thank you for giving us your thoughtful comments/suggestions. We have responded to them one by one, and revised our manuscript according to the manner as below. We are looking forward to your positive consideration of the publication in our manuscript. Best regards, Takahisa Gono, corresponding author Reviewer #1: 1. I agree with authors lower SP-D levels is potentially relevant to the rapid progressive course of anti-MDA5 antibody-associated ILD and the level could be low at the disease diagnosis. However, is there any speculation on the issue which patients with anti-ARS had a higher level of SP-D among other MSAs? Since the elevated serum levels of SP-D could be attributed to an increase in SP-D production by regenerating alveolar type II pneumocytes, did the patients with anti-ARS have already widespread findings of ILD on chest CT at diagnosis or have longer disease duration from diagnosis of ILD? Response: I appreciate your valuable comments. As the reviewer suggested, the elevated serum levels of SP-D could be dependent on the degree of regenerating alveolar type II pneumocytes and/or that of destruction in alveolar capillaries. To answer the reviewer’s suggestions, we compared disease duration at diagnosis of ILD among three groups: anti-MDA5 antibody-positive group, anti-ARS antibody-positive group and, double-negative group. The median disease duration (interquartile range [IQR]) was 2 months (1-3), 3 months (1-8), and 3 months (1-6) in anti-MDA5 antibody-positive group, anti-ARS antibody-positive group and, double-negative group, respectively. The disease duration was significantly shorter in anti-MDA5 antibody-positive group than in anti-ARS antibody-positive group (P = 0.0002) or double-negative group (P = 0.0005). The range of disease duration in anti-ARS antibody-positive group was 0-122 months; longer than that of double-negative group with 0-88 months, although there was no significant difference (P = 0.82) between the two groups. In terms of the severity of pulmonary dysfunction with %vital capacity (VC), the median value (IQR) of %VC was lower in anti-ARS antibody-positive group: 70.2% (60-85), than in double-negative group: 84.9% (66-98) (P = 0.0002) or anti-MDA5 antibody positive group: 81% (66-98) (P = 0.0005) (revised Figure 2B). On the other hand, there was no significant difference (P = 0.53) between double-negative group and anti-MDA5 antibody-positive group. Unfortunately, we have no data regarding chest HRCT score. These findings indicated that the serum levels of SP-D in anti-ARS antibody-positive group were influenced by more widespread damage of ILD as well as the longer disease duration of ILD. To describe this point, we have added the following sentences as below. In line 168 to 182 on page 7 to 8, “We also compared disease duration and pulmonary function among the three groups. With regard to disease duration at diagnosis of PM/DM-associated ILD, the median disease duration (IQR) was significantly shorter in anti-MDA5 antibody-positive group: 2 months (1-3), than in anti-ARS antibody-positive group: 3 months (1-8) (P = 0.0002) or double-negative group: 3 months (1-6) (P = 0.0005). The range of disease duration in anti-ARS antibody-positive group was 0-122 months; longer than that of double-negative group with 0-88 months, although there was no significant difference of the median disease duration (P = 0.82) between the two groups. In terms of the severity of pulmonary dysfunction with %vital capacity (VC), the median value (IQR) of %VC was lower in anti-ARS antibody positive group: 70.2% (60-85), than in double-negative group: 84.9% (66-98) (P = 0.0002) or anti-MDA5 antibody positive group: 81% (66-98) (P = 0.0005) (Figure 2B). On the other hand, there was no significant difference (P = 0.53) between anti-MDA5 antibody-positive group and double-negative group. These results indicated more widespread damage of ILD as well as longer disease duration in anti-ARS antibody-positive group than the other two groups.” In line 222 to 229 on page 9, “Histopathological differences of ILD at diagnosis of PM/DM-associated ILD might contribute to the behavior of serum SP-D levels in each MSA group. In this study, the disease duration was significantly longer in in anti-ARS antibody-positive group or double-negative group than in anti-MDA5-positive group. In addition, the median value of %vital capacity was lower in anti-ARS antibody-positive group than in double-negative group or anti-MDA5 antibody-positive group. These findings might indicate that chronic damage and remodelling of peripheral pulmonary structure was more apparent in anti-ARS antibody-positive group, causing translocation of SP-D molecules from alveolar epithelium to blood vessels much more.” Reviewer #2: 1. Please provide intra-class comparison of non-survivor vs. survivor in each MSA group. Response: Please see Figure 1B, 1C and 1D. We have provided the intra-class comparison of serum SP-D levels between non-survivors and survivors in each MSA group. #2 It should be emphasized that serum SP-D is approved as a laboratory test for clinical use and easily available at clinical practice in Japan, however it is approved only for research use in many countries other than Japan including Europe and North America. Also, it should be pronounced that serum SP-D might be beneficial for patients outside Japan if the test were approved for clinical use. Response: As the reviewer indicated, actually, the measurement of SP-D is not yet available at clinical practice in many countries. In the future, however, it should be validated whether the measurement of serum SP-D levels is beneficial for prediction of outcomes in patients with PM/DM-associated ILD if the test were approved for clinical use in many countries over the world. To emphasize this issue, we added the following sentences as below. In line 237 to 244 on page 10, “SP-D can be measured as a laboratory test for clinical use in Japan based on the unique Japanese health insurance system. The measurement of SP-D is not yet available at clinical practice in many countries. Further study is required to investigate…, and to validate whether the measurement of serum SP-D levels is beneficial for prediction of outcomes in each MSA among patients with PM/DM-associated ILD in daily practice if the test is approved for clinical use in many countries over the world.” #3 Please enrich discussion about reasons for the difference in serum SP-D levels by MSA. Especially, focusing on mechanisms of translocation of SP-D molecules from alveolar epithelium to serum and on difference in damage of peripheral pulmonary structure by MSAs would be preferable. Response: Thank you for your constructive suggestion. Histopathological analysis was not conducted in our study. As the reviewer indicated, we speculate that the histopathological difference of ILD at diagnosis may contribute to the behavior of serum SP-D levels in each MSA. Furthermore, we analyzed disease duration and severity of pulmonary dysfunction with %vital capacity among the three groups, as the reviewer#1 suggested. The disease duration at diagnosis is significantly shorter in anti MDA-5 antibody-positive group than in anti-ARS antibody-positive group or double negative group. In terms of %vital capacity, the median value (interquartile range [IQR]) of %vital capacity was lower in anti-ARS antibody positive group: 70.2% (60-85), than in double-negative group: 84.9% (66-98) (P = 0.0002) or anti-MDA5 antibody positive group: 81% (66-98) (P = 0.0005) (revised Figure 2B). On the other hand, there was no significant difference (P = 0.53) between double-negative group and anti-MDA5 antibody-positive group. These findings might indicate that chronic damage and remodelling of peripheral pulmonary structure was more apparent in anti-ARS antibody-positive group, causing translocation of SP-D molecules from alveolar epithelium to serum much more. To describe this point, we have added the following sentences as below. In line 168 to 182 on page 7 to 8, “We also compared disease duration and pulmonary function among the three groups. With regard to disease duration at diagnosis of PM/DM-associated ILD, the median disease duration (IQR) was significantly shorter in anti-MDA5 antibody-positive group: 2 months (1-3), than in anti-ARS antibody-positive group: 3 months (1-8) (P = 0.0002) or double-negative group: 3 months (1-6) (P = 0.0005). The range of disease duration in anti-ARS antibody-positive group was 0-122 months; longer than that of double-negative group with 0-88 months, although there was no significant difference of the median disease duration (P = 0.82) between the two groups. In terms of the severity of pulmonary dysfunction with %vital capacity (VC), the median value (IQR) of %VC was lower in anti-ARS antibody positive group: 70.2% (60-85), than in double-negative group: 84.9% (66-98) (P = 0.0002) or anti-MDA5 antibody positive group: 81% (66-98) (P = 0.0005) (Figure 2B). On the other hand, there was no significant difference (P = 0.53) between anti-MDA5 antibody-positive group and double-negative group. These results indicated more widespread damage of ILD as well as longer disease duration in anti-ARS antibody-positive group than the other two groups.” In line 222 to 229 on page 9, “Histopathological differences of ILD at diagnosis of PM/DM-associated ILD might contribute to the behavior of serum SP-D levels in each MSA group. In this study, the disease duration was significantly longer in in anti-ARS antibody-positive group or double-negative group than in anti-MDA5-positive group. In addition, the median value of %vital capacity was lower in anti-ARS antibody-positive group than in double-negative group or anti-MDA5 antibody-positive group. These findings might indicate that chronic damage and remodelling of peripheral pulmonary structure was more apparent in anti-ARS antibody-positive group, causing translocation of SP-D molecules from alveolar epithelium to blood vessels much more.” Attachments Attachment Submitted filename: Responce to Reviewers comments.docx https://doi.org/10.1371/journal.pone.0234523.r002
28 May 2020 Decision Letter - Minghua Wu, Editor Evaluation of usefulness in surfactant protein D as a predictor of mortality in myositis-associated interstitial lung disease PONE-D-20-07783R1 Dear Dr. Gono 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, Minghua Wu, M.D., Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0234523.r003
Formally Accepted
1 Jun 2020 Acceptance Letter - Minghua Wu, Editor PONE-D-20-07783R1 Evaluation of usefulness in surfactant protein D as a predictor of mortality in myositis-associated interstitial lung disease Dear Dr. Gono: 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. Minghua Wu Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0234523.r004

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 .