PONE-D-20-06891

Complement activation profile of patients with primary focal segmental glomerulosclerosis

PLOS ONE

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Kind regards,

Zhanjun Jia

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: 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: No

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The article ‘Complement activation profile of patients with primary focal segmental glomerulosclerosis’ written by Dr. Huang Jing illustrated that activation of complement system was positively correlated with more severe clinical manifestations, compromised kidney function and poor renal outcomes. There exists systemic activation of complement in human primary FSGS, possibly via alternative and classical pathways. The large cohort of patients, proper study design and more than 2 years follow-up make the study sound and reliable. The study paved the way for possible complement monoclonal antibody used in FSGS. However, there’s still some minor revisions for the article.

Minor revisions

1. An English revision, including grammars and spelling, like para 1 line 3: ’presents with’, para 1 line 5’characters’, para 2 line 6 ‘reduction…prevention’, para 2 line 9 ’having’ and so on, is mandatory.

2. Please show the demographic information of the gender and age-matched healthy control group.

3. As shown in table 1, serum albumin level varied from 14.4g/L to 27.8g/L and 24h protein excretions were within massive range. Therefore, complement components could also leaked out into the urine. Is it necessary to correct plasma complement level with serum albumin level?

Reviewer #2: This is a nice study to evaluate the plasma and urinary complement profile of patients with primary FSGS. But the results section of the manuscript is too complicated and not easy to follow. I would be easy read if the authors could simplify results section. In addition, for the conclusion of "The activation of complement system was associated with the clinical manifestations, kidney pathological damage, and renal outcomes", I do not find enough data to support the activation of complement system was associated with the clinical manifestations and kidney pathological damage. I have following comments which should be considered.

1. The definition of complete remission was stricter than other studies which was that proteinuria ≤ 0.3 g/24h with stable serum creatinine and serum albumin great than 35 g/L. Why the authors define complete remission as proteinuria less than or equal to 0.15 g/24h with stable serum creatinine?

2. The endpoint of renal outcome is end stage of renal disease, please clarify the definition.

3. I would suggest move the sentence of "The pathological variants of the 70 patients were defined according to the Columbia classification [2], which included 23 tip variant, 23 NOS variant, 21 cellular variant, 1 collapsing variant and 2 advanced FSGS (defined as the percentage of sclerosis/total glomeruli over 75%)" to renal histopathology section to make easy understanding.

4. A total of 70 patients were included in this study, but in Table 1 only 57 patients were evaluated the response to treatment, please clarify the reason of not evaluation 70 patients. The authors mentioned treatment in the method section, but did not include them in Table 1. It would helpful to include them in Table 1.

5. For Cox regression, did the authors included urinary Bb, C3a and C5a in the same model? Urinary Bb was correlated with C3a and C5a, therefore, the issue of collinearity will produce when all of them were included in the same model.

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Reviewer #1: Yes: Ruochen Che

Reviewer #2: No

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Complement activation profile of patients with primary focal segmental glomerulosclerosis

PONE-D-20-06891R1

Dear Dr. huang,

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,

Zhanjun Jia

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

**********

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

Reviewer #1: Yes

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 #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

**********

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: (No Response)

Reviewer #2: The authors have addressed my questions. Thanks the authors considered my comments and revised the manuscript. I don't have additional question.

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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: Yes: Ruochen Che

Reviewer #2: No