CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder

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We evaluated transcription factor mRNA levels in CD4+ T cells as predictive biomarkers of phenoconversion in iRBD, showing that among the transcription factors mRNA levels analysed, STAT1, GATA3 and FOXP3 mRNA levels may be used to predict phenoconversion. In particular, we found that CD4+ T cells from converters had higher STAT1, and lower GATA3 and FOXP3 mRNA levels. According to ROC curve analysis STAT1 levels provided a good discrimination, GATA3 levels an excellent discrimination of future converters and not-converters, while discrimination provided by FOXP3 levels was acceptable." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-683", "name": "CD4+ T-cell transcription factors as early predictors of phenoconversion..." } } ] } Home Browse CD4+ T-cell transcription factors as early predictors of phenoconversion... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Pinoli M, Terzaghi M, Marino F et al. CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.12688/f1000research.163212.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Data Note Revised CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] Previously titled: The importance of early biomarkers in the identification of neurodegenerative disorders Monica Pinoli 1 , Michele Terzaghi 2 , Franca Marino https://orcid.org/0000-0003-1837-7810 1 , Cristoforo Comi https://orcid.org/0000-0002-6862-9468 1,3 , Maurizio Versino 4 , Marco Cosentino https://orcid.org/0000-0002-6978-7775 1 Monica Pinoli 1 , Michele Terzaghi 2 , [...] Franca Marino https://orcid.org/0000-0003-1837-7810 1 , Cristoforo Comi https://orcid.org/0000-0002-6862-9468 1,3 , Maurizio Versino 4 , Marco Cosentino https://orcid.org/0000-0002-6978-7775 1 PUBLISHED 06 Oct 2025 Author details Author details 1 Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy 2 Unit of Sleep Medicine and Epilepsy, IRCCS Mondino Foundation, Pavia, Italy 3 Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy 4 Department of Medicine and Surgery, University of Insubria, Varese, Italy Monica Pinoli Roles: Conceptualization, Data Curation, Formal Analysis, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Michele Terzaghi Roles: Validation, Visualization Franca Marino Roles: Validation, Visualization Cristoforo Comi Roles: Validation, Visualization Maurizio Versino Roles: Validation, Visualization Marco Cosentino Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Project Administration, Resources, Supervision, Validation, Visualization, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Bioinformatics gateway. This article is included in the Cell & Molecular Biology gateway. This article is included in the Retinal Physiology collection. Abstract In this datanote we present data from 31 iRBD (idiopathic Rapid eye movement (REM) sleep Behaviour Disorder) patients followed throughout three years to assess their eventual phenoconversion to Parkinson’s disease and other established neurodegenerative conditions. iRBD is a prodromal condition of neurological pathologies such as Parkinson’s disease. We evaluated transcription factor mRNA levels in CD4+ T cells as predictive biomarkers of phenoconversion in iRBD, showing that among the transcription factors mRNA levels analysed, STAT1, GATA3 and FOXP3 mRNA levels may be used to predict phenoconversion. In particular, we found that CD4+ T cells from converters had higher STAT1, and lower GATA3 and FOXP3 mRNA levels. According to ROC curve analysis STAT1 levels provided a good discrimination, GATA3 levels an excellent discrimination of future converters and not-converters, while discrimination provided by FOXP3 levels was acceptable. READ ALL READ LESS Keywords Early biomarkers, neurodegenerative disorders, Parkinson’s disease; CD4+ T lymphocytes; Transcription factors; Gene expression Corresponding Author(s) Marco Cosentino ( [email protected] ) Close Corresponding author: Marco Cosentino Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Pinoli M et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Pinoli M, Terzaghi M, Marino F et al. CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.12688/f1000research.163212.2 ) First published: 10 Jul 2025, 14 :683 ( https://doi.org/10.12688/f1000research.163212.1 ) Latest published: 06 Oct 2025, 14 :683 ( https://doi.org/10.12688/f1000research.163212.2 ) Revised Amendments from Version 1 In the present version, the title has been modified to make it more consistent with the content of the study, the abstract has been expanded to include a summary of the main results and the introduction has been reworked to better highlight the innovative nature of the research ad its connection to our previous publications. In the present version, the title has been modified to make it more consistent with the content of the study, the abstract has been expanded to include a summary of the main results and the introduction has been reworked to better highlight the innovative nature of the research ad its connection to our previous publications. See the authors' detailed response to the review by Tommaso Schirinzi See the authors' detailed response to the review by Adawiya J. Haider READ REVIEWER RESPONSES Introduction Rapid eye movement (REM) sleep behaviour disorder (RBD) is a REM-phase parasomnia, typically associated with neurodegenerative disorders (38-75% 1 , 2 ). iRBD (idiopathic Rapid eye movement (REM) sleep Behaviour Disorder) is a prodromal condition in the process underlying synucleinopathies, including Parkinson’s disease (PD). The risk for PD conversion in people with iRBD is estimated around 43% at five years. 3 The data included here are from a study 3 that evaluated whether transcription factor genes TBX21 , STAT1 , STAT3 , STAT4 , STAT6 , RORC , GATA3 , FOXP3 , and NR4A2 mRNA levels in CD4+ T cells could represent predictive biomarkers of phenoconversion in iRBD patients. To this end, we performed a follow-up of the iRBD subjects enrolled in previous research, 4 with the aim to identify three years later who was eventually phenoconverted towards a frank neurodegenerative condition. The study by Di Francesco et al. (2021) 4 showed that in iRBD subjects CD4+ T cells exhibit a peculiar molecular signature strongly resembling cells from PD patients, while the study by Pinoli et al. (2024) 5 thereafter revealed that STAT1, GATA3 and FOXP3 mRNA levels in CD4+ T cells are promising predictive biomarkers of phenoconversion in iRBD patients. Indeed, converters showed higher expression levels of STAT1, and lower levels of GATA3 and FOXP3. We also found higher percentages of monocytes in converters versus not converters. The implications of these transcription factors in the neuroinflammatory process are clearly evinced also from the contribution they make to the differentiation of Th1 (STAT1), Th2 (GATA3) and Treg (FOXP3) phenotypes. Namely, it was demonstrated that peripheral blood of PD patients had increased Th1 and decreased Th2 and Treg. 6 We decided to focus on the study of molecular markers to identify early variations that could allow us to identify individuals who will develop PD, before lesions develop. Future studies will be necessary to further explore the role of these markers and subsequently develop targeted drugs for tailored therapy. Data reported in this paper have been previously analysed in Pinoli et al. (2024) and De Francesco et al. (2021). Materials and methods Ethical statement The Ethics Committee of the Neurological Institute “C. Mondino” of Pavia approved the protocol (number 2021008499, 10/02/2021) and all the participants signed a written informed consent before enrolment. Participants 31 patients were followed at the Sleep Center of the Neurological Institute “C. Mondino” of Pavia. The clinical evaluation included: motor symptoms, assessed by means of the Unified Parkinson’s Disease Rating Scale (UPDRS) part III 7 ; cognitive function, by the Mini Mental State Examination (MMSE) 8 , 9 ; constipation and orthostatic hypotension by means of the Scale for Outcomes in Parkinson’s disease-Autonomic (SCOPA-AUT) 7 ; depressive symptoms, by means of the Hamilton Rating Scale for Depression (HAM-D). 10 At the original enrolment, 5 each patient provided a venous blood sample, which was processed to isolate CD4+ T cells, according to an established procedure. 6 Subjects with iRBD were followed prospectively with periodic in-person evaluations to diagnose phenoconversion, i.e., parkinsonism, DLB and MSA. Isolation of CD4+ T Cells Peripheral blood mononuclear cells were separated by Ficoll-Paque Plus density gradient centrifugation; then CD4+ T cells were obtained by immunomagnetic sorting. Cell viability was 95% ± 1% (range, 90%–98%), and purity was 98% ± 2% (range, 97%–100%). Expression of the TF genes TBX21, STAT1, STAT3, STAT4, STAT6, RORC, GATA3, FOXP3, and NR4A2 was measured by real-time polymerase chain reaction. Real-time polymerase chain reaction assay For real-time PCR assays of CD4+ T cells, at least 50,000 CD4+ T cells were resuspended in PerfectPure RNA lysis buffer (5 Prime GmbH, Hamburg, Germany), and total RNA was extracted by PerfectPure RNA Cell Kit™ (5 Prime GmbH, code 2302340). The amount of extracted RNA was estimated by spectrophotometry at λ = 260 nm. Total mRNA was then reverse-transcribed using a random primer and a high-capacity cDNA RT kit (Applied Biosystems, code 4368813), and the resulting amount of cDNA was estimated by spectrophotometry at λ = 260 nm. Real-Time PCR reactions were then started with 1 μM cDNA. At the beginning, we always loaded 1 μg/μl of cDNA per reaction (final reaction mix volume + sample = 20 μl). This means that for each reaction we load 2 μl of aqueous solution containing the cDNA (therefore, 2 μg of cDNA in total). The following thermal protocol was used for each sample: 20 s at 95°C (x 1, hot start); 2-step cycles as follows: 1 s at 95°C, 20 s at 60°C (x 40). All the reagents (probes and mix) were used according to the manufacturer’s instructions ( www.bio-rad.com ). Ethics and consent Ethical approval and consent were not required. Data availability FigShare: “The importance of early biomarkers in the identification of neurodegenerative disorders”. Doi: 10.6084/m9.figshare.28603907 11 The project contains the following underlying data: • Raw data of patients collected during enrolment and follow-up (.xls) • Patients were labeled with an anonymized sample ID number. Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Acknowledgements The authors wish to thank all the patients and their relatives and caregivers who accepted to be enrolled in the study, as well as all the nurses and colleagues who helped in recruitment, clinical assessment and collection of demographic and clinical data. The authors wish to express their gratefulness to Doctor Gaetano Malomo, MD, Department of Brain and Behavioral Sciences, University of Pavia, Pavia (I), who is responsible for updating and maintaining the iRBD patients archive, and to Professor Giovanni Veronesi, MD, PhD, Department of Medicine and Surgery, University of Insubria, Varese (I), who kindly supervised in part the statistical analysis. References 1. Gagnon JF, Postuma RB, Mazza S, et al. : Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases. Lancet Neurol. 2006; 5 : 424–432. Publisher Full Text 2. Sforza E, Krieger J, Petiau C: REM sleep behavior disorder: clinical and physiopathological findings. Sleep Med. Rev. 1997; 1 : 57–69. PubMed Abstract | Publisher Full Text 3. Galbiati M, Verga L, Giora E, et al. : The risk of neurodegeneration in REM sleep behavior disorder: A systematic review and meta-analysis of longitudinal studies. Sleep Med. Rev. 2019; 43 : 37–46. PubMed Abstract | Publisher Full Text | Free Full Text 4. De Francesco E, Terzaghi M, Storelli E, et al. : CD4+ T-cell Transcription Factors in Idiopathic REM Sleep Behavior Disorder and Parkinson’s Disease. Mov. Disord. 2021; 36 : 225–229. PubMed Abstract | Publisher Full Text 5. Pinoli M, Terzaghi M, Marino F, et al. : CD4+ T-cell transcription factors predict phenoconversion in idiopathic rapid eye movement sleep behavior disorder. Future Sci. OA. 2024 31; 10 (1): 2418821. PubMed Abstract | Publisher Full Text | Free Full Text 6. Kustrimovic N, Comi C, Magistrelli L, et al. : Parkinson’s disease patients have a complex phenotypic and functional Th1 bias: cross-sectional studies of CD4+ Th1/Th2/T17 and Treg in drug-naïve and drug-treated patients. J. Neuroinflammation. 2018; 15 : 205. PubMed Abstract | Publisher Full Text | Free Full Text 7. Goetz CG, Tilley BC, Shaftman SR, et al. : Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov. Disord. 2008; 23 : 2129–2170. PubMed Abstract | Publisher Full Text 8. Folstein MF, Folstein SE, McHugh PR: "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 1975; 12 : 189–198. Publisher Full Text 9. Visser M, Marinus J, Stiggelbout AM, et al. : Assessment of autonomic dysfunction in Parkinson’s disease: the SCOPA-AUT. Mov. Disord. 2004; 19 : 1306–1312. Publisher Full Text 10. Hamilton M: A rating scale for depression. J. Neurol. Neurosurg. Psychiatry. 1960; 23 : 56–62. PubMed Abstract | Publisher Full Text | Free Full Text 11. FigShare: “The importance of early biomarkers in the identification of neurodegenerative disorders”. The project contains the following underlying data: Raw data; data legend. Publisher Full Text Comments on this article Comments (1) Version 2 VERSION 2 PUBLISHED 06 Oct 2025 Revised Reviewer Response 30 Oct 2025 Adawiya haider , University of Technology, Baghdad, Iraq 30 Oct 2025 Reviewer Response Thanks to all authors who response to all my comments. regards Competing Interests: No, competing interests Thanks to all authors who response to all my comments. regards Thanks to all authors who response to all my comments. regards Competing Interests: No, competing interests Close Report a concern Comment ADD YOUR COMMENT Author details Author details 1 Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy 2 Unit of Sleep Medicine and Epilepsy, IRCCS Mondino Foundation, Pavia, Italy 3 Movement Disorders Centre, Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy 4 Department of Medicine and Surgery, University of Insubria, Varese, Italy Monica Pinoli Roles: Conceptualization, Data Curation, Formal Analysis, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Michele Terzaghi Roles: Validation, Visualization Franca Marino Roles: Validation, Visualization Cristoforo Comi Roles: Validation, Visualization Maurizio Versino Roles: Validation, Visualization Marco Cosentino Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Project Administration, Resources, Supervision, Validation, Visualization, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 06 Oct 2025, 14:683 https://doi.org/10.12688/f1000research.163212.2 version 1 Published: 10 Jul 2025, 14:683 https://doi.org/10.12688/f1000research.163212.1 Copyright © 2025 Pinoli M et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Pinoli M, Terzaghi M, Marino F et al. CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.12688/f1000research.163212.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 06 Oct 2025 Revised Views 0 Cite How to cite this report: Haider AJ. Reviewer Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.188922.r420598 ) The direct URL for this report is: https://f1000research.com/articles/14-683/v2#referee-response-420598 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 28 Oct 2025 Adawiya J. Haider , University of Technology, Baghdad, Baghdad, Iraq Approved VIEWS 0 https://doi.org/10.5256/f1000research.188922.r420598 Thanks, authors have ... Continue reading READ ALL Thanks, authors have made all comments. regards Competing Interests: No competing interests were disclosed. Reviewer Expertise: Nanotechnology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Haider AJ. Reviewer Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.188922.r420598 ) The direct URL for this report is: https://f1000research.com/articles/14-683/v2#referee-response-420598 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Schirinzi T. Reviewer Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.188922.r420597 ) The direct URL for this report is: https://f1000research.com/articles/14-683/v2#referee-response-420597 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 07 Oct 2025 Tommaso Schirinzi , University of Rome Tor Vergata, Via Cracovia, Roma, Italy Approved VIEWS 0 https://doi.org/10.5256/f1000research.188922.r420597 No comments, The ... Continue reading READ ALL No comments, The manuscript is improved. Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Schirinzi T. Reviewer Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.188922.r420597 ) The direct URL for this report is: https://f1000research.com/articles/14-683/v2#referee-response-420597 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 10 Jul 2025 Views 0 Cite How to cite this report: Haider AJ. Reviewer Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.179522.r411090 ) The direct URL for this report is: https://f1000research.com/articles/14-683/v1#referee-response-411090 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 17 Sep 2025 Adawiya J. Haider , University of Technology, Baghdad, Baghdad, Iraq Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.179522.r411090 1. The title needs revision; should the name match the content of the text paper? 2-Abstract: not clear and should be more scientific and include some of the results in this paper. 3- The introduction needs expansion in ... Continue reading READ ALL 1. The title needs revision; should the name match the content of the text paper? 2-Abstract: not clear and should be more scientific and include some of the results in this paper. 3- The introduction needs expansion in the last paragraph and focuses on the novelty of this work. 4- This work needs more expansion and agreement with the previous research. Is the rationale for creating the dataset(s) clearly described? No Are the protocols appropriate and is the work technically sound? No Are sufficient details of methods and materials provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Nanotechnology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Haider AJ. Reviewer Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.179522.r411090 ) The direct URL for this report is: https://f1000research.com/articles/14-683/v1#referee-response-411090 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 01 Oct 2025 Monica Pinoli , University of Insubria, Varese, Italy 01 Oct 2025 Author Response Dear Dr. Haider, Thank you for your valuable suggestions that provided us with insights to improve our manuscript. 1. The title needs revision → The title has been modified to ... Continue reading Dear Dr. Haider, Thank you for your valuable suggestions that provided us with insights to improve our manuscript. 1. The title needs revision → The title has been modified to better describe the content of the paper. 2-Abstract: not clear and should be more scientific and include some of the results in this paper → The abstract has been extended to include the core results. 3- The introduction needs expansion in the last paragraph and focuses on the novelty of this work → We changed some parts of the introduction, adding sentences which should better clarify the novelty of this work. 4- This work needs more expansion and agreement with the previous research → Previous research related to this work has been now more extensively mentioned and discussed to make clearer the novelty and relevance of the present contents. Dear Dr. Haider, Thank you for your valuable suggestions that provided us with insights to improve our manuscript. 1. The title needs revision → The title has been modified to better describe the content of the paper. 2-Abstract: not clear and should be more scientific and include some of the results in this paper → The abstract has been extended to include the core results. 3- The introduction needs expansion in the last paragraph and focuses on the novelty of this work → We changed some parts of the introduction, adding sentences which should better clarify the novelty of this work. 4- This work needs more expansion and agreement with the previous research → Previous research related to this work has been now more extensively mentioned and discussed to make clearer the novelty and relevance of the present contents. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 01 Oct 2025 Monica Pinoli , University of Insubria, Varese, Italy 01 Oct 2025 Author Response Dear Dr. Haider, Thank you for your valuable suggestions that provided us with insights to improve our manuscript. 1. The title needs revision → The title has been modified to ... Continue reading Dear Dr. Haider, Thank you for your valuable suggestions that provided us with insights to improve our manuscript. 1. The title needs revision → The title has been modified to better describe the content of the paper. 2-Abstract: not clear and should be more scientific and include some of the results in this paper → The abstract has been extended to include the core results. 3- The introduction needs expansion in the last paragraph and focuses on the novelty of this work → We changed some parts of the introduction, adding sentences which should better clarify the novelty of this work. 4- This work needs more expansion and agreement with the previous research → Previous research related to this work has been now more extensively mentioned and discussed to make clearer the novelty and relevance of the present contents. Dear Dr. Haider, Thank you for your valuable suggestions that provided us with insights to improve our manuscript. 1. The title needs revision → The title has been modified to better describe the content of the paper. 2-Abstract: not clear and should be more scientific and include some of the results in this paper → The abstract has been extended to include the core results. 3- The introduction needs expansion in the last paragraph and focuses on the novelty of this work → We changed some parts of the introduction, adding sentences which should better clarify the novelty of this work. 4- This work needs more expansion and agreement with the previous research → Previous research related to this work has been now more extensively mentioned and discussed to make clearer the novelty and relevance of the present contents. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Schirinzi T. Reviewer Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.179522.r399771 ) The direct URL for this report is: https://f1000research.com/articles/14-683/v1#referee-response-399771 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 23 Aug 2025 Tommaso Schirinzi , University of Rome Tor Vergata, Via Cracovia, Roma, Italy Approved VIEWS 0 https://doi.org/10.5256/f1000research.179522.r399771 This manuscript presented a full dataset including clinical and biological data derived from iRBD patients who eventually converted to PD. The effort is valuable and the methodological issues are pretty addressed. I suggest avoiding repeating the RBD abbreviation ... Continue reading READ ALL This manuscript presented a full dataset including clinical and biological data derived from iRBD patients who eventually converted to PD. The effort is valuable and the methodological issues are pretty addressed. I suggest avoiding repeating the RBD abbreviation and indicating references for the statements regarding the risk of phenoconversion. Further, I recommend clearly stating the main aim of this publication. Is the rationale for creating the dataset(s) clearly described? Partly Are the protocols appropriate and is the work technically sound? Yes Are sufficient details of methods and materials provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Biological issues of PD and movement disorders I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Schirinzi T. Reviewer Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.179522.r399771 ) The direct URL for this report is: https://f1000research.com/articles/14-683/v1#referee-response-399771 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 01 Oct 2025 Monica Pinoli , University of Insubria, Varese, Italy 01 Oct 2025 Author Response Dear Dr. Schirinzi, we want to thank you for your suggestions, that help us to improve our manuscript. Avoiding repeating the RBD abbreviation → Repetition of abbreviations have ... Continue reading Dear Dr. Schirinzi, we want to thank you for your suggestions, that help us to improve our manuscript. Avoiding repeating the RBD abbreviation → Repetition of abbreviations have been eliminated. Indicate the reference for the statements regarding the risk of phenoconversion → We added the reference. I recommend clearly stating the main aim of this publication → We modified the introduction and tried to better highlight the aim. Dear Dr. Schirinzi, we want to thank you for your suggestions, that help us to improve our manuscript. Avoiding repeating the RBD abbreviation → Repetition of abbreviations have been eliminated. Indicate the reference for the statements regarding the risk of phenoconversion → We added the reference. I recommend clearly stating the main aim of this publication → We modified the introduction and tried to better highlight the aim. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 01 Oct 2025 Monica Pinoli , University of Insubria, Varese, Italy 01 Oct 2025 Author Response Dear Dr. Schirinzi, we want to thank you for your suggestions, that help us to improve our manuscript. Avoiding repeating the RBD abbreviation → Repetition of abbreviations have ... Continue reading Dear Dr. Schirinzi, we want to thank you for your suggestions, that help us to improve our manuscript. Avoiding repeating the RBD abbreviation → Repetition of abbreviations have been eliminated. Indicate the reference for the statements regarding the risk of phenoconversion → We added the reference. I recommend clearly stating the main aim of this publication → We modified the introduction and tried to better highlight the aim. Dear Dr. Schirinzi, we want to thank you for your suggestions, that help us to improve our manuscript. Avoiding repeating the RBD abbreviation → Repetition of abbreviations have been eliminated. Indicate the reference for the statements regarding the risk of phenoconversion → We added the reference. I recommend clearly stating the main aim of this publication → We modified the introduction and tried to better highlight the aim. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (1) Version 2 VERSION 2 PUBLISHED 06 Oct 2025 Revised Reviewer Response 30 Oct 2025 Adawiya haider , University of Technology, Baghdad, Iraq 30 Oct 2025 Reviewer Response Thanks to all authors who response to all my comments. regards Competing Interests: No, competing interests Thanks to all authors who response to all my comments. regards Thanks to all authors who response to all my comments. regards Competing Interests: No, competing interests Close Report a concern Comment ADD YOUR COMMENT keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 2 (revision) 06 Oct 25 read read Version 1 10 Jul 25 read read Tommaso Schirinzi , University of Rome Tor Vergata, Via Cracovia, Italy Adawiya J. Haider , University of Technology, Baghdad, Iraq Comments on this article All Comments (1) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Haider A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 28 Oct 2025 | for Version 2 Adawiya J. Haider , University of Technology, Baghdad, Baghdad, Iraq 0 Views copyright © 2025 Haider A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Thanks, authors have made all comments. regards Competing Interests No competing interests were disclosed. Reviewer Expertise Nanotechnology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Haider AJ. Peer Review Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.188922.r420598) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-683/v2#referee-response-420598 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Schirinzi T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 07 Oct 2025 | for Version 2 Tommaso Schirinzi , University of Rome Tor Vergata, Via Cracovia, Roma, Italy 0 Views copyright © 2025 Schirinzi T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions No comments, The manuscript is improved. Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Schirinzi T. Peer Review Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.188922.r420597) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-683/v2#referee-response-420597 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Haider A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 17 Sep 2025 | for Version 1 Adawiya J. Haider , University of Technology, Baghdad, Baghdad, Iraq 0 Views copyright © 2025 Haider A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions 1. The title needs revision; should the name match the content of the text paper? 2-Abstract: not clear and should be more scientific and include some of the results in this paper. 3- The introduction needs expansion in the last paragraph and focuses on the novelty of this work. 4- This work needs more expansion and agreement with the previous research. Is the rationale for creating the dataset(s) clearly described? No Are the protocols appropriate and is the work technically sound? No Are sufficient details of methods and materials provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? No Competing Interests No competing interests were disclosed. Reviewer Expertise Nanotechnology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 01 Oct 2025 Monica Pinoli, University of Insubria, Varese, Italy Dear Dr. Haider, Thank you for your valuable suggestions that provided us with insights to improve our manuscript. 1. The title needs revision → The title has been modified to better describe the content of the paper. 2-Abstract: not clear and should be more scientific and include some of the results in this paper → The abstract has been extended to include the core results. 3- The introduction needs expansion in the last paragraph and focuses on the novelty of this work → We changed some parts of the introduction, adding sentences which should better clarify the novelty of this work. 4- This work needs more expansion and agreement with the previous research → Previous research related to this work has been now more extensively mentioned and discussed to make clearer the novelty and relevance of the present contents. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Haider AJ. Peer Review Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.179522.r411090) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-683/v1#referee-response-411090 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Schirinzi T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 23 Aug 2025 | for Version 1 Tommaso Schirinzi , University of Rome Tor Vergata, Via Cracovia, Roma, Italy 0 Views copyright © 2025 Schirinzi T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This manuscript presented a full dataset including clinical and biological data derived from iRBD patients who eventually converted to PD. The effort is valuable and the methodological issues are pretty addressed. I suggest avoiding repeating the RBD abbreviation and indicating references for the statements regarding the risk of phenoconversion. Further, I recommend clearly stating the main aim of this publication. Is the rationale for creating the dataset(s) clearly described? Partly Are the protocols appropriate and is the work technically sound? Yes Are sufficient details of methods and materials provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Biological issues of PD and movement disorders I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (1) Author Response 01 Oct 2025 Monica Pinoli, University of Insubria, Varese, Italy Dear Dr. Schirinzi, we want to thank you for your suggestions, that help us to improve our manuscript. Avoiding repeating the RBD abbreviation → Repetition of abbreviations have been eliminated. Indicate the reference for the statements regarding the risk of phenoconversion → We added the reference. I recommend clearly stating the main aim of this publication → We modified the introduction and tried to better highlight the aim. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Schirinzi T. Peer Review Report For: CD4+ T-cell transcription factors as early predictors of phenoconversion in idiopathic rapid eye movement sleep behaviour disorder [version 2; peer review: 2 approved] . F1000Research 2025, 14 :683 ( https://doi.org/10.5256/f1000research.179522.r399771) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-683/v1#referee-response-399771 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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