Associated factors of health-related quality of life in Indonesian Women with Systemic Lupus Erythematosus: A cross-sectional within-cohort analysis

Euphemia Seto Anggraini Widyastuti; Josephine Lavina; Gabriel Justin Darmajaya; Stevent Sumantri

doi:10.1371/journal.pone.0341989

Peer Review History

Original SubmissionJanuary 23, 2026
11 Mar 2026 Decision Letter - Wesam Gouda, Editor Dear Dr. Sumantri, 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. Please submit your revised manuscript by Apr 25 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.. 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.. 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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.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 Reviewer #3: No ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** Reviewer #1: Manuscript Number: PONE-D-26-01165 Title: Predictors of Health-Related Quality of Life in Indonesian Women with Systemic Lupus Erythematosus: A Cross-Sectional Within-Cohort Analysis General Comments This manuscript investigates the factors influencing health-related quality of life (HRQoL) in a specific cohort of Indonesian women with SLE. The study identifies sleep quality, anxiety, and age as significant independent predictors of QoL, explaining 36.1% of the variance. The finding that clinical disease activity (MEX-SLEDAI) and corticosteroid dose did not significantly correlate with QoL in this predominantly low-activity cohort is particularly noteworthy and highlights a potential "disconnect" between clinical markers and patient well-being. While the study is well-structured and uses validated instruments, several areas regarding statistical interpretation and local context require clarification to meet the standards of PLOS ONE. Specific Comments and Revision Requirements 1. Methodology and Statistical Stability • Variable Definition: The authors combine "Anxiety/Depression" into a single dichotomous variable. Given that the DASS-21 provides distinct subscales, please clarify the rationale for this grouping. • Subgroup Size: Only 3 subjects (4%) were identified as having anxiety or depression. The authors must address the statistical limitations of drawing strong conclusions or high beta coefficients (-21.402) from such a small subgroup. • Multicollinearity: Considering the known overlap between sleep disturbances and psychological distress, did the authors test for multicollinearity (e.g., Variance Inflation Factor) in their regression model? 2. Clinical and Diagnostic Tools • MEX-SLEDAI Rationale: The manuscript provides a strong justification for using the MEX-SLEDAI in resource-limited settings. To enhance the "Materials and Methods" section, explicitly state if specialized immunological assays (e.g., anti-dsDNA) were unavailable at the study site or if the tool was chosen for its practical utility in Southeast Asian clinical practice. • Pain Scale Thresholds: The authors use a 40mm VAS cutoff to define "severe" pain. Please provide a specific citation supporting this threshold as a marker for functional impairment specifically within the SLE population. 3. Results Interpretation • Variance Explanation: The model explains 36.1% of HRQoL variance. The Discussion should more robustly address the remaining 63.9%, perhaps speculating on the roles of social support, cultural stigma, or permanent organ damage which were not measured in this study. It is recommended that the authors include theses study limitation in the discussion. • Education Levels: In Table 2, the p-value for education is exactly 0.050. The authors should clarify if they consider this statistically significant or a trend, as the text describes it as having "influenced QoL". 4. Discussion and Contextual Depth • Age and Quality of Life: The finding that younger age predicts lower QoL is a highlight of the paper. The authors are encouraged to expand on the "burden of a life interrupted" by providing more specific local context regarding the social and professional expectations for young women in Indonesia. • Socioeconomic Factors: 77.3% of the participants had incomes above the minimum wage. The authors should discuss how the recruitment from a private hospital clinic might skew the socioeconomic representation compared to the broader Indonesian SLE population. 5. Actionable Recommendations • Intervention Specificity: The conclusion advocates for "psychosocial and sleep interventions". To increase the paper's impact, the authors should briefly detail which components of Cognitive-Behavioral Therapy for Insomnia (CBT-I) and anxiety management are most feasible for implementation within the Indonesian healthcare framework. Reviewer #2: This article is beneficial to improve current care of SLE. But the following points need a further clarification. 1. The reference should be added : Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4. PMID: 2748771. 2. Do "Hours of sleep per night" ( in the Pittsburgh Sleep Quality Index) relate with QoL? 3. Why male lupus is not investigated in this study ? ( Please explain it ) Reviewer #3: 1)The title does not reflect the primary objective of this study as stated in the Introduction “impact of sleep disturbances and psychiatric symptoms on daily function…” 2)This was a cross-sectional study so wont be able to establish the causal and effect relationship. Please revise the term “effects/predictors” to “association/associated factors” 2)Method -Please clarify whether the questionnaires were in English or Indonesian language. Please provide the validation study if the questionnaires were translated. -What was the sampling method? -The objective also include the impact on daily function. What was the tool used to determine/ measure the daily function of the patients? -The variables (sleep pattern, HRQoL, VAS, MEX-SLEDAI) were categorized. But in the statistical analysis, there was no chi square performed and/or multivariate logistic regression performed to determine the relationships between these variables. -Please clarify which one of the following was the dependant variable in this study. Sleep pattern or HRQoL? ****** what does this mean?). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.). 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 For information about this choice, including consent withdrawal, please see our For information about this choice, including consent withdrawal, please see our For information about this choice, including consent withdrawal, please see our Privacy Policy..--> Reviewer #1: Yes: Yi-Hsing ChenYi-Hsing ChenYi-Hsing ChenYi-Hsing Chen Reviewer #2: Yes: Chung-Jen ChenChung-Jen ChenChung-Jen ChenChung-Jen Chen Reviewer #3: 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 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. Attachments Attachment Submitted filename: Reviewer report to PLOS ONe-PONE-D-26-01165-20260303.docx https://doi.org/10.1371/journal.pone.0341989.r001
Revision 1
21 Mar 2026 Author Response 1. Variable Definition: The authors combine "Anxiety/Depression" into a single dichotomous variable. Given that the DASS-21 provides distinct subscales, please clarify the rationale for this grouping. We thank the reviewer for this insightful comment. The decision to combine anxiety and depression into a single dichotomous variable was based on both clinical and statistical considerations. First, in our cohort, the prevalence of clinically significant symptoms was low (n=3 for depression and anxiety). Notably, these cases overlapped entirely (comorbidity), making it statistically impossible to treat them as independent predictors in a multivariate model without causing significant multicollinearity issues. Second, from an integrative clinical perspective, we aimed to identify a general 'psychosocial distress' signal. Given the high degree of internal consistency and correlation between DASS-21 subscales, this grouping allowed for a more robust and stable linear regression model, yielding a clearer β-coefficient for the impact of psychological health on HRQoL." 2. Only 3 subjects (4%) were identified as having anxiety or depression. The authors must address the statistical limitations of drawing strong conclusions or high beta coefficients (-21.402) from such a small subgroup. We acknowledge the reviewer’s concern regarding the small subgroup (n=3) for the Anxiety/Depression variable and the resulting high beta coefficient. We agree that a beta of -21.402 is sensitive to the small number of participants in this category. However, the statistical significance (p=0.001) despite the small n indicates a very large effect size—specifically, a mean HRQoL difference of nearly 30 points (85.42 vs 56.66). While we cannot claim this coefficient is a precise population constant, it serves as a robust indicator of the disproportionate impact psychological distress has on HRQoL in SLE. We have revised the manuscript to explicitly label this as a study limitation and have adjusted our language to be exploratory rather than definitive. 3. Considering the known overlap between sleep disturbances and psychological distress, did the authors test for multicollinearity (e.g., Variance Inflation Factor) in their regression model? We thank the reviewer for highlighting the potential for multicollinearity between sleep quality and psychological distress. We agree that these domains often overlap in SLE populations. To address this, we conducted a formal collinearity diagnostic during the model-building process. The Variance Inflation Factor (VIF) for all predictors in the final model ranged from [1.025] to [1.055], which is well below the conservative threshold of 2.5 (and the standard threshold of 10). Furthermore, the Tolerance values were all above 0.8. These results indicate that multicollinearity did not bias our regression estimates or the observed beta coefficients. We have added this detail to the 'Statistical Analysis' section of the revised manuscript. 4. MEX-SLEDAI Rationale: The manuscript provides a strong justification for using the MEX-SLEDAI in resource-limited settings. To enhance the "Materials and Methods" section, explicitly state if specialized immunological assays (e.g., anti-dsDNA) were unavailable at the study site or if the tool was chosen for its practical utility in Southeast Asian clinical practice. We have revised the manuscript accordingly. 5. Pain Scale Thresholds: The authors use a 40mm VAS cutoff to define "severe" pain. Please provide a specific citation supporting this threshold as a marker for functional impairment specifically within the SLE population. We have revised the manuscript accordingly. 6. The finding that younger age predicts lower QoL is a highlight of the paper. The authors are encouraged to expand on the "burden of a life interrupted" by providing more specific local context regarding the social and professional expectations for young women in Indonesia. We appreciate the suggestion to expand on the impact of SLE on younger patients. We have added a section to the Discussion detailing the specific sociocultural pressures faced by young Indonesian women, particularly regarding marriage, fertility, and the dual expectations of professional and domestic roles, which contribute to the lower HRQoL observed in this demographic. 7. Socioeconomic Factors: 77.3% of the participants had incomes above the minimum wage. The authors should discuss how the recruitment from a private hospital clinic might skew the socioeconomic representation compared to the broader Indonesian SLE population. The reviewer correctly notes the socioeconomic skew of our cohort. We have addressed this in the Discussion and Limitations sections by clarifying that our recruitment from a private hospital likely resulted in a higher-income representation. we have expanded on how this might 'buffer' some HRQoL impacts compared to the broader, more economically diverse Indonesian SLE population. 8. Do "Hours of sleep per night" ( in the Pittsburgh Sleep Quality Index) relate with QoL? We thank the reviewer for this query regarding sleep duration. While the Global PSQI score was used in our primary model to capture the multidimensional nature of sleep disturbances (including quality, latency, and daytime dysfunction), we performed a post-hoc correlation analysis between 'Actual Hours of Sleep' (PSQI Component 3) and HRQoL. We found that 'Hours of Sleep' alone did not significantly correlate with HRQoL (r = -0.221, p = 0.057). This suggests that in our cohort, sleep fragmentation and poor sleep quality—rather than sheer sleep deprivation—are the primary drivers of reduced quality of life. This aligns with existing literature suggesting that SLE-related fatigue is often non-restorative regardless of sleep duration." 9. Why male lupus is not investigated in this study ? ( Please explain it ) The decision to focus exclusively on female patients was made to ensure methodological and phenotypic homogeneity within a relatively small cohort (N=75) 10. This was a cross-sectional study so wont be able to establish the causal and effect relationship. Please revise the term “effects/predictors” to “association/associated factors” We have revised the manuscript accordingly. 11. Please clarify whether the questionnaires were in English or Indonesian language. Please provide the validation study if the questionnaires were translated. We appreciate the opportunity to clarify the linguistic validation of our instruments. All questionnaires used in this study (PSQI, DASS-21, and the HRQoL tool) were administered in the Indonesian language. We used previously validated Indonesian versions of these scales to ensure cultural and linguistic competence. Reference list updated accordingly. 12. What was the sampling method? We have updated the sampling methods (consecutive) in the manuscript accordingly. 13. The objective also include the impact on daily function. What was the tool used to determine/ measure the daily function of the patients? The reviewer is correct that daily function is a key objective. In this study, 'daily function' was assessed as a core component of the Health-Related Quality of Life (HRQoL) instrument. Specifically, we analyzed the [Physical Functioning/Activity] domains of the [Lupus QoL], which measures the extent to which health limits physical activities such as self-care, walking, and social roles. 14. The variables (sleep pattern, HRQoL, VAS, MEX-SLEDAI) were categorized. But in the statistical analysis, there was no chi square performed and/or multivariate logistic regression performed to determine the relationships between these variables. We would like to clarify our statistical approach. While variables such as sleep quality and psychological distress were categorized in the descriptive tables (Table 1 and 2) to facilitate clinical interpretation (e.g., 'Poor' vs. 'Good' sleep), they were treated as continuous variables in the multivariate linear regression analysis. This approach was chosen to maximize statistical power and avoid the loss of information inherent in dichotomization. Therefore, a linear regression was appropriate to determine the predictors of the continuous HRQoL score, rather than a logistic regression. 15. Please clarify which one of the following was the dependant variable in this study. Sleep pattern or HRQoL? We apologize for any ambiguity. In this study, Health-Related Quality of Life (HRQoL) was the dependent variable. Sleep patterns (PSQI), psychological distress (DASS-21), and clinical markers (MEX-SLEDAI) were treated as the independent variables (predictors). We have updated the manuscript accordingly. Attachments Attachment Submitted filename: Revision Letter and Responses.docx https://doi.org/10.1371/journal.pone.0341989.r002
6 Apr 2026 Decision Letter - Wesam Gouda, Editor Associated Factors of Health-Related Quality of Life in Indonesian Women with Systemic Lupus Erythematosus: A Cross-Sectional Within-Cohort Analysis PONE-D-26-01165R1 Dear Dr. Sumantri, 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. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. 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For more information, please contact onepress@plos.org. Kind regards, Wesam Gouda, MD,PhD Academic Editor PLOS One Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed Reviewer #3: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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.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 Reviewer #3: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** Reviewer #1: The manuscript is technically sound, the data supports the conclusions, and the authors have addressed all my comments appropriately. The "Key Messages" summary box effectively distills the clinical impact for the readership. Though the authors have handled a small-sample-size study. the strength of this paper lies not in its generalizability to all SLE patients, but in its specific insights into the Indonesian outpatient context. Reviewer #2: This article is beneficial to improve current care of female SLE. I have no further comments. [In the future, male SLE is worthy of investigation] Reviewer #3: Thank you for the revised manuscript All of the comments and queries have been addressed by thr authors. ****** what does this mean?). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.). 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 For information about this choice, including consent withdrawal, please see our For information about this choice, including consent withdrawal, please see our For information about this choice, including consent withdrawal, please see our Privacy Policy..--> Reviewer #1: Yes: Yi-Hsing ChenYi-Hsing ChenYi-Hsing ChenYi-Hsing Chen Reviewer #2: Yes: Chung-Jen ChenChung-Jen ChenChung-Jen ChenChung-Jen Chen Reviewer #3: No ******** https://doi.org/10.1371/journal.pone.0341989.r003
Formally Accepted
Acceptance Letter - Wesam Gouda, Editor PONE-D-26-01165R1 PLOS One Dear Dr. Sumantri, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Wesam Gouda Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0341989.r004

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