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ACADEMIC EDITOR: Major revision

Please submit your revised manuscript by Feb 11 2026 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.

• A 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'.
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We look forward to receiving your revised manuscript.

Kind regards,

Marwan Salih Al-Nimer, MD, PhD

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 include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files.’

3. Thank you for stating the following financial disclosure:

“This study received grant from Ramathibodi Hospital, Mahidol university”

Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

4. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match.

When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.

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Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition).

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7. Please upload a copy of Figure 1, to which you refer in your text on page 9. If the figure is no longer to be included as part of the submission please remove all reference to it within the text.

8. Please include a copy of Table 4 which you refer to in your text on page 4.

9. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

Additional Editor Comments:

This manuscript is not well prepared. It needs a major revision

1: Revise the introduction and supplement it with updated references.

2: Methods are not clear. Rewrite the methods, specify the eligibility, inclusion, exclusion, the parametes.......etc.

3; The results were without tables and figures???????

4: Rewrite the discussion. The authors added only one reference to the discussion????

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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?

Reviewer #1: Partly

Reviewer #2: Partly

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

Reviewer #1: No

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

Reviewer #1: No

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: The analysis isn´t enough descriptive. Previous comorbidity pathologic conditions doesn´t mention if earliest disease manifestations can be related to the so called initial adult-onset immunodeficiency nor if there are previous treatments achieved during early comorbidities, evolution or manifestations of disease. Analysis doesn´t mention changes for expresión of activation markers among immunocompetent population nor if there is a shift from a Th1/Th2, inflammatory/anti-inflammatory profile of population, and even in the secretion of cytokine profiles of subpopulations. It would be appropriate to know if such immunologic adult-onset disease parameters are related to clinical course changes from active to remission of disease. There is also a lack of other inflammatory and/or fibrin- or coagulation-related factors, such as ferritin, D-dimer, PLT and thrombin-related times which would perpetuate inflammatory profiles. In my opinión, there are some issues that remain to be defined in a context-dependent manner as in maintaining active treatment in order to avoid progression after ending treatment. In summary changes in remission states have their own positive clinical characteristics at remission contrary to those at initial adult-onset diagnosis but it means to check clinical course of disease along time in order to maintain anti-inflammatory changes.

Reviewer #2: In this manuscript, the authors investigate the correlation between anti–interferon‑γ autoantibody titers measured by inhibitory ELISA and clinical disease activity, as well as inflammatory biomarkers in adult‑onset immunodeficiency. The topic is clinically important, especially given the high prevalence of anti‑IFN‑γ autoantibody–associated immunodeficiency in Southeast Asia and the ongoing need for reliable biomarkers for disease monitoring. The study is generally well-written and contains meaningful data; however, several major and minor issues should be addressed before the manuscript can be considered for publication.

Major Comments

1. The manuscript repeatedly refers to Table 1–4 and Figure 1, but these materials do not appear in the provided document. This significantly impairs the ability to evaluate data presentation, statistical validity, interpretation of ROC curves and diagnostic performance. Therefore, please ensure that all tables and figures referenced in the text are included, properly formatted, and placed within the main manuscript, or uploaded as separate supporting files.

2. The study is described as retrospective, nested within a prospective cohort, but essential methodological details require clarification. Were samples collected and analyzed at uniform time points for all patients? Were the biomarkers measured at the same visit as disease activity assessment? These clarifications are needed to ensure internal validity and avoid bias.

3. Inclusion and exclusion criteria need further explanation. Whether all consecutive patients with anti‑IFN‑γ auto Abs were included. Whether disease activity distribution (40 active vs 29 remission samples) might reflect selection bias. Clarification is required to validate the generalizability of the results.

4. There is no information on duration of illness, prior antimicrobial or immunosuppressive therapy, timing of relapse/remission cycles. These variables could significantly influence biomarkers (e.g., CRP, ESR, IL‑6) and may confound interpretation of disease activity. Therefore, this information should be included.

5. The Methods section requires further clarification and expansion, particularly regarding Inhibitory ELISA methodology, cytokine assays and immune cell population analysis. At present, essential methodological details are missing, which limits the reproducibility and interpretability of the results.

6. The manuscript reports AUC, cutoffs, sensitivity, specificity, etc., but confidence intervals (CIs) are missing for many key metrics. CIs are essential for interpreting robustness and reproducibility. Logistic regression analysis is briefly mentioned, but the regression model structure, variable selection strategy, model diagnostics (multicollinearity, goodness‑of‑fit), are insufficiently described.

7. The study concludes that combining biomarkers improves diagnostic performance; however, there is limited discussion on clinical feasibility, particularly since IL‑6 testing may not be routinely available. The impact of comorbidities—e.g., infections, anemia, hepatic or renal dysfunction—on CRP, ESR, ALP, or WBC levels should be acknowledged. How these factors may confound biomarker interpretation should be discussed

8. Discussion should address clinical implementation challenges

Minor Comments

1. The table on comorbidities is only described in text. Once tables are added, ensure demographic and clinical characteristics are clearly presented.

2. Some thresholds (e.g., IL‑6 >16) should indicate units explicitly (pg/mL). Make units consistent throughout.

3. The discussion is generally sound, but could be strengthened by comparing predictive performance with prior studies more explicitly and adding comments on how inhibitory ELISA may complement or replace indirect ELISA in clinical practice.

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Reviewer #1: Yes: Luis Molto Delgado

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Manuscript PONE 025 58456 dec 2025.pdf

Dear Dr. Laisuan,

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.

ACADEMIC EDITOR: Minor revision

Please submit your revised manuscript by February 22, 2026. 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.

• A 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 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: https://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,

Marwan Salih Al-Nimer, MD, PhD

Academic Editor

PLOS One

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

2. 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:

Retype the references according to the PLoS ONE guideline

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

[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 ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

Correlation between clinical disease activity and interferon-Υ autoantibody titers measured by inhibitory ELISA, and inflammatory biomarkers in adult-onset immunodeficiency associated with anti-interferon-Υ autoantibodies

PONE-D-25-58456R2

Wannada Laisuan

Dear Dr. Wannada Laisuan,

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,

Marwan Salih Al-Nimer, MD, PhD

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments: