Evaluating Value of Lactic Dehydrogenase in Anti-MDA5-positive Dermatomyositis Associated with Interstitial Lung Disease

Evaluating Value of Lactic Dehydrogenase in Anti-MDA5-positive Dermatomyositis Associated with Interstitial Lung Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluating Value of Lactic Dehydrogenase in Anti-MDA5-positive Dermatomyositis Associated with Interstitial Lung Disease Wenhan Huang, Feifeng Ren, Kechen Qian, Yanqiu Jiang, Yichen zhang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7551189/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective This study aimed to investigate the relationship between lactic dehydrogenase (LDH) and anti-melanoma differentiation-associated gene 5 antibodies-positive dermatomyositis (anti-MDA5-positive DM) complicated by interstitial lung disease (ILD). Method 168 anti-MDA5-positive DM patients with ILD underwent comprehensive evaluation, including LDH, anti-Ro-52 antibodies, serum ferritin determination, and lung high-resolution CT. Results The level of LDH were significantly elevated in anti-MDA5-positive DM patients compared with control group (p < 0.01). Anti-Ro-52-positive patients demonstrated significantly higher LDH levels compared to anti-Ro-52-negative patients (p < 0.01). Patients with elevated serum ferritin exhibited markedly increased LDH levels compared with those with lower serum ferritin (p < 0.01). After treatment, LDH levels significantly increased in patients with ILD deterioration (p < 0.01), whereas LDH decreased in patients with ILD amelioration or stabilization (p < 0.01). The LDH levels were significantly elevated in the death group compared to the survival group before treatment (p = 0.02). Conclusion 1. The LDH levels were affected by anti-Ro-52 antibodies and serum ferritin. 2. The ILD severity of anti-MDA5-positive DM patients positively correlated with LDH, suggesting that LDH might serve as an effective assessment indicator to evaluate the changes in ILD in these patients. 3. Elevated LDH levels were a crucial indicator of poor prognosis in anti-MDA5-positive DM patients, warranting close attention from rheumatologists. anti-MDA5-positive DM lactic dehydrogenase interstitial lung disease anti-Ro-52 antibodies serum ferritin Figures Figure 1 Figure 2 Figure 3 Introduction Sato et al. [ 1 , 2 ] initially characterized anti-melanoma differentiation-associated gene 5 antibodies-positive dermatomyositis (anti-MDA5-positive DM), this disease has garnered considerable clinical attention owing to its propensity for rapidly progressive interstitial lung disease (RP-ILD) development, culminating in elevated mortality rates [ 3 , 4 ]. Undoubtedly, pulmonary assessment in anti-MDA5-positive DM patients is the core of the clinical work. Contemporary evaluation modalities predominantly encompass chest CT and pulmonary function assessments. Furthermore, patients demonstrating elevated serum Krebs Von den Lungen-6 levels exhibit heightened predisposition toward RP-ILD development [ 5 ]. Nevertheless, an urgent clinical imperative persists for straightforward, efficacious indicator facilitating ILD severity assessment in anti-MDA5-positive DM patients. Lactic dehydrogenase represents a pivotal redox enzyme catalyzing pyruvate-to-lactate conversion. LDH is abundantly distributed in tissue of heart, liver, skeletal muscle, and lungs. When cells were damaged or ruptured, enhanced permeability facilitates LDH release into systemic circulation, elevating serum concentrations. Consequently, LDH serves as a significant tissue injury biomarker. Currently, LDH detection finds widespread application in myocardial infarction [ 6 ], liver injury [ 7 ], and tumors [ 8 ]. Recent investigations have validated LDH's crucial role in pulmonary injury evaluation, with LDH levels closely correlating with acute respiratory distress syndrome prognosis [ 9 ]. Nevertheless, LDH research regarding anti-MDA5-positive DM-associated interstitial lung disease remains limited. This manuscript retrospectively analysed 168 anti-MDA5-positive DM patients from the department of Rheumatology and Immunology at the Second Affiliated Hospital of Chongqing Medical University, explored the relationship between LDH and ILD so as to provide assistance for clinical guidance. Method From September 2015 to July 2025, 168 anti-MDA5-positive DM patients with ILD were hospitalized at the Second Affiliated Hospital of Chongqing Medical University. Patients comorbid with cardiac disease, hepatitis, skeletal muscle and myocardial involvement, pulmonary infections, and malignancies were excluded. Controls comprised health examination subjects at the same institution. In accordance with the Helsinki Declaration, all patients or relatives provided informed consent for participation and data publication. The ethics committee of the Second Affiliated Hospital of Chongqing Medical University approved this study. LDH levels were quantified utilizing the lactic acid substrate methodology. Anti-MDA5 and anti-Ro-52 antibodies were tested using an OMRMUN assay kits (EUROIMMUN, Beijing, China). Serum ferritin were measured by chemiluminescence method using an Access Ferritin kit (Beckman Coulter, CA, USA). Grouping: (1) LDH levels were evaluated by comparing 168 patients with anti-MDA5-positive DM before treatment in the control group. (2) High-resolution pulmonary computed tomography was performed in 168 patients with anti-MDA5-positive DM before and after treatment to assess the relationship between LDH and ILD. Based on radiological findings, patients were dichotomized: Group 1 (n = 116): showed reduction or no significant changes in pulmonary lesions after treatment; Group 2 (n = 52): exhibited newly emerged infiltrative shadows in the lungs on post-treatment imaging, defined as disease progression, excluding factors such as infection, pulmonary embolism, or heart failure [ 10 ]. All CT evaluations were conducted by an experienced radiologist and espiratory specialist. (3) The 168 anti-MDA5-positive DM patients were stratified according to anti-Ro-52 antibody status, ferritin concentrations, and prognostic outcomes to examine LDH variations. Statistical analysis All analyses utilized SPSS 19.0 (IBM, Armonk, NY, USA). Normally distributed data were presented as mean ± standard deviation, while non-normal distribution data were expressed as median and interquartile range. Mann-Whitney test were used to compare two groups. Wilcoxon test was used to compare the difference before and after treatment. Multiple comparisons were assessed by Kruskal-Wallis test. Values of p < 0.05 was considered significant. Results 1. Baseline Information The normal group encompassed 160 individuals (52 males, 108 females; male:female ratio 1:2.07; mean age 51.3 ± 9.6 years). A total of 168 anti-MDA5-positive DM patients, including 57 male and 111 female patients (male:female ratio 1:1.95; mean age 51.7 ± 13.0 years). The LDH level was 143.5 ± 30.2 U/L in the control group and 319 [250.2, 394] U/L in patients with anti-MDA5-positive DM before treatment, which was significantly elevated versus controls (p < 0.01, Fig. 1 ). 2. The Relationship between LDH and Anti-Ro52 antibody 168 anti-MDA5-positive DM patients were dichotomized based on anti-Ro-52 antibody status. Results demonstrated: (1) Among the 111 patients with anti-Ro-52 antibody, the LDH level before treatment was 336 [(267, 403)] U/L. In contrast, among the 57 patients without anti-Ro-52 antibody, the LDH level before treatment was 299.6 ± 107.7 U/L. A statistically significant difference was observed between the two groups, p < 0.01. (2) The LDH level of patients with positive anti-Ro-52 antibodies was 279 [193, 482] U/L after treatment, which was not significantly different from that before treatment (p = 0.45). (3) The LDH level of patients without anti-Ro-52 antibodies was 203 [156, 776] U/L after treatment, which was significantly reduced compare to that before treatment (p < 0.01, Table 1 ). Table 1 Comparison of LDH levels in patients with anti-MDA5-positive DM with or without anti-Ro-52 antibodies before and after treatment Anti-Ro-52 antibodies positive n = 111 Anti-Ro-52 antibodies negative n = 57 P value Before treatment (U/L ) 336 [(267, 403)] 299.6 ± 107.7 <0.01 After treatment (U/L) 279 [(193, 482)] 203 [(156, 776)] <0.01 P value 0.45 <0.01 3. Relationship between LDH and serum ferritin 168 anti-MDA5-positive DM patients were categorized into three groups based on their ferritin levels. Group 1: serum ferritin<500ng/ml, (n = 69), Group 2: 500ng/ml ≤ serum ferritin < 1000ng/ml, (n = 39), Group 3: 1000ng/ml ≤ serum ferritin ≤ 1500ng/ml, (n = 60). LDH level of patients before treatment in Group 1 was 278.2 ± 84.6 U/L, significantly lower than that of patients in Groups 2 and 3 (Group 2: 340.4 ± 82.9 U/L; Group 3: 382.5 [(301.3, 492.5)] U/L; respectively, p<0.01) (Fig. 2 A). After treatment, patients in Group 1 exhibited an LDH level of 193 [(158, 232)] U/L, which was significantly lower than that before treatment, p < 0.01 (Fig. 2 B). The LDH level of patients in Group 2 after treatment was 234 [(186, 318)] U/L, markedly diminished compared to that before treatment, p < 0.01 (Fig. 2 C). The LDH level of patients in Group 3 after treatment was 435.5 [(285, 577)] U/L, and the difference was not statistically significant compared with that before treatment, p = 0.06 (Fig. 2 D). 4. Relationship between LDH and ILD To elucidate LDH-ILD correlations before and after treatment, we divided 168 anti-MDA5-positive DM patients into two groups. Group 1, encompassing patients with improved or stabilized interstitial lung disease after treatment (n = 115), and Group 2, comprising patients with deteriorated interstitial lung disease after treatment (n = 53). In group 1, the LDH level of patients significantly decreased after treatment (before treatment: 297 [(242, 392)] U/L vs. after treatment: 201 [(174, 244)] U/L, p < 0.01, Fig. 3 A). Conversely, Group 2 demonstrated marked LDH elevation relative to baseline when interstitial lung disease deteriorated (before treatment: 342 [(279.5, 431.5)] U/L vs. after treatment: 512 [(395, 664)] U/L, p < 0.01, Fig. 3 B). 5. Relationship between LDH and Prognosis 168 anti-MDA5-positive DM patients were categorized into a survival group (n = 126) and a deceased group (n = 42) based on their prognosis. (1) The LDH level before treatment in the survival group was 299.5 [(241.5, 392.3)] U/L, which was significantly lower than that in the deceased group (345.0 [(298.8, 472.0)] U/L, p = 0.02). (2) After treatment, the LDH level in the survival group decreased to 203.5 [(174.8, 259.3)] U/L, which was significantly lower than that before treatment (p < 0.01). (3) In the deceased group, the LDH level after treatment increased to 534.5 [(444.3, 666.5)] U/L, which was significantly higher than than that before treatment (p < 0.01). (Table 2 ) Table 2 Comparison of LDH levels before and after treatment in patients with anti-MDA5-positive DM based on prognosis Survival group n = 126 Deceased group n = 42 P value Before treatment (U/L ) 299.5 [(241.5, 392.3)] 345.0 [(298.8, 472.0)] 0.02 After Treatment (U/L) 203.5 [(174.8, 259.3)] 534.5 [(444.3, 666.5)] <0.01 P value <0.01 <0.01 Discussion Anti-MDA5-positive DM patients developing RP-ILD frequently manifest poor prognosis and elevated mortality rates, commanding escalating clinical attention. However, lung lesion assessments in anti-MDA5-positive DM remain relatively scarce with inherent constraints, such as radiation exposure caused by repeat chest CT scan in a short period of time, critical patients couldn't complete pulmonary function assessments adequately; and KL-6 testing practicality diminishes owing to economic constraints and temporal limitations. Consequently, identifying straightforward, innocuous, and efficacious biomarkers for evaluating ILD severity in anti-MDA5-positive DM patients assumes paramount significance. This investigation concentrated on analyzing LDH-ILD correlations in anti-MDA5-positive DM patients, endeavoring to furnish innovative clinical assessment methodologies. Our findings demonstrated that the LDH levels in anti-MDA5-positive DM patients withILD before treatment were markedly elevated compared with those in control group, indicating that LDH is an important indicator that shouldn’t be ignored. Subsequently, we explored LDH correlations with anti-MDA5-positive DM comprehensively. Firstly, extensive research has validated the pivotal role of anti-Ro-52 antibodies in inflammatory myopathies. Patients with anti-Ro-52 antibodies positive were more likely to develop rapidly progressive interstitial lung disease [ 11 ], subcutaneous and mediastinal emphysema [ 12 ], and pharyngeal lesions [ 13 ]. Our study revealed that the LDH level before treatment was significantly elevated in patients with anti-Ro-52 antibodies than in those without anti-Ro-52 antibodies, confirming LDH-anti-Ro-52 antibodies associations in anti-MDA5-positive DM patients. Furthermore, no significant differences were found in the LDH level of patients positive for anti-Ro-52 antibodies before and after treatment, whereas the level of LDH in patients negative for anti-Ro-52 antibodies decreased significantly after treatment. This suggested anti-Ro-52 antibodies modulate therapeutic responsiveness, potentially attributable to more severe interstitial lung disease in anti-Ro-52-positive patients. Secondly, serum ferritin is also an important evaluation indicator for anti-MDA5-positive DM. Takahisa et al. [ 14 ] suggested that anti-MDA5-positive DM represents macrophage activation occurring in the lungs, distinguished by pronounced ferritin elevation. Through ferritin level stratification, we discerned that LDH levels in anti-MDA5-positive DM patients exhibited concordance with ferritin levels, showing a direct correlation between inflammatory magnitude and LDH elevation. Additionally, We found that under different inflammatory states, the difference of LDH levels of anti-MDA5 positive DM patients before and after treatment were also observed. Patients with serum ferritin < 500 ng/ml and 500–1000 ng/ml demonstrated significant post-treatment LDH attenuation versus baseline, signifying a better treatment response in mild-to-moderate inflammatory states. Conversely, when serum ferritin was between 1000 and 1500 ng/ml, no significant difference was found in LDH levels before and after treatment, indicating glucocorticoid and immunosuppressants have no improvement effect on LDH in severe inflammatory conditions. This finding bears profound clinical implications, underscoring the imperative for rheumatologists to judiciously modulate inflammatory burden in anti-MDA5-positive DM patients, thereby attenuating disease activity and improving the prognosis. Given anti-MDA5-positive DM's predominant lung manifestations, we prioritized LDH-ILD correlational analysis. Our data indicated that LDH levels diminish relative to baseline when ILD lesions were improved or stabilized post-treatment. Conversely, progressive ILD deterioration and intensified pulmonary injury precipitate substantial tissue LDH efflux into systemic circulation, markedly elevating serum concentrations versus pretreatment values. These observations establish positive correlation between LDH levels and ILD severity in anti-MDA5-positive DM patients. On the one hand, extracellular LDH functions as a damage-associated molecular pattern, promoting the release of inflammatory factors and exacerbating pulmonary inflammation. On the other hand, LDH's fundamental physiological role is to catalyze pyruvic acid into lactic acid. A high concentration of lactic acid in tissues can activate TGF-β, inducing myofibroblast differentiation and thus accelerating the pulmonary fibrosis process [ 15 ]. Our study confirmed that LDH was a simple yet effective biomarker to evaluate the changes in ILD in patients with anti-MDA5-positive DM. Finally, regarding prognosis, the LDH levels were substantially elevated before treatment in the deceased group than in the survival group. After treatment, LDH levels in the deceased group escalated further, while exhibiting marked amelioration in the survival group, indicating LDH’s prognostic significance in anti-MDA5-positive DM. Analogous findings [ 16 , 17 ] in COVID-19 patients characterized by acute lung injury, it was found that non survivors had significantly higher levels of LDH than survivors. As a result, LDH was regarded as an important indicator for evaluating patients' respiratory function and predicting their prognosis. Combined with the above findings and our study, it was strongly confirmed that the pivotal role of LDH in lung lesions assessment in anti-MDA5-positive DM patients. Several limitations warrant acknowledgement. Firstly, our study exclusively examined LDH’s relationship with anti-MDA5-positive DM, precluding characterization of other inflammatory myopathy types, such as antisynthetase syndrome. Secondly, mechanistic exploration remains superficial, requiring deeper investigation. Lastly, single-center clinical data necessitate multicenter validation with expanded sample sizes. In conclusion, this study elucidated LDH’s associations with serological markers, lung interstitial lesions, and prognosis in anti-MDA5-positive DM patients, furnishing clinically relevant insights and establishing groundwork for subsequent research. Declarations Conflict of interest: There is no conflict of interest of this study. Disclosure statement: There is no potential conflicts of interest of each author and this manuscript is approved by all authors for publication. Data availability statement ： All data relevant to the study are included in the article. Acknowledgments ： I would like to thank my wife Dan Wang and my baby daughter Yuti Huang. It's your endless love that makes me fearless. Authors consent: This manuscript was approved by all of the authors. References Sato S, Hirakata M, Kuwana M et al .: Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum 2005;52(5):1571-6. https://doi.org/10.1002/art.21023. 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Medicine (Baltimore). 2021;100(4):e24441. https://doi: 10.1097/MD.0000000000024441. Gupta GS. The Lactate and the Lactate Dehydrogenase in Inflammatory Diseases and Major Risk Factors in COVID-19 Patients. Inflammation. 2022;45(6):2091-2123. https://doi: 10.1007/s10753-022-01680-7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7551189","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":520036114,"identity":"cbef8926-30cd-462c-9f9b-339da65a962b","order_by":0,"name":"Wenhan Huang","email":"","orcid":"","institution":"The Second Affiliated Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wenhan","middleName":"","lastName":"Huang","suffix":""},{"id":520036115,"identity":"b07d488a-9287-4e00-8f37-68da1da7c9c1","order_by":1,"name":"Feifeng Ren","email":"","orcid":"","institution":"The Second Affiliated Hospital of 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1","display":"","copyAsset":false,"role":"figure","size":962582,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of LDH levels between control group and patients with anti-MDA5-positive DM before treatment, p \u0026lt; 0.01.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7551189/v1/7b9808d264d6ad97ba91b676.png"},{"id":92233647,"identity":"86cf44d8-5430-4436-8ae7-67757d8c8f73","added_by":"auto","created_at":"2025-09-26 06:59:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1590380,"visible":true,"origin":"","legend":"\u003cp\u003eRelationship between LDH and serum ferritin. (A) Levels of LDH before treatment grouped by serum ferritin. (B) Changes in LDH levels before and after treatment for patients in Group 1 (serum ferritin＜500ng/ml, n=69). (C) Changes in LDH levels before and after treatment for patients in Group 2 (500g/ml≤serum ferritin \u0026lt; 1000ng/ml, n=39). (D) Changes in LDH levels before and after treatment for patients in Group 3 (1000g/ml≤serum ferritin≤1500ng/ml, n=60)\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7551189/v1/038ab63bbc70ad570b2d8559.png"},{"id":92233649,"identity":"eb61e60a-5096-4efa-88bf-50b641a9a4e3","added_by":"auto","created_at":"2025-09-26 06:59:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":622461,"visible":true,"origin":"","legend":"\u003cp\u003eLDH fluctuations before and after treatment in 168 anti-MDA5-positive DM patients. (A) Group 1: ILD was improved or stabilized after treatment (n=115), (B) Group 2: ILD was aggravated after treatment (n=53), p＜0.01.\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7551189/v1/44885374002d910698436161.png"},{"id":92236107,"identity":"92b1a4c8-b939-413e-a8f1-7884ef7c70bb","added_by":"auto","created_at":"2025-09-26 07:24:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3969005,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7551189/v1/d17bfffb-8250-4cf2-af3f-f18bf57bcccc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eEvaluating Value of Lactic Dehydrogenase in Anti-MDA5-positive Dermatomyositis Associated with Interstitial Lung Disease\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSato et al. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] initially characterized anti-melanoma differentiation-associated gene 5 antibodies-positive dermatomyositis (anti-MDA5-positive DM), this disease has garnered considerable clinical attention owing to its propensity for rapidly progressive interstitial lung disease (RP-ILD) development, culminating in elevated mortality rates [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Undoubtedly, pulmonary assessment in anti-MDA5-positive DM patients is the core of the clinical work. Contemporary evaluation modalities predominantly encompass chest CT and pulmonary function assessments. Furthermore, patients demonstrating elevated serum Krebs Von den Lungen-6 levels exhibit heightened predisposition toward RP-ILD development [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Nevertheless, an urgent clinical imperative persists for straightforward, efficacious indicator facilitating ILD severity assessment in anti-MDA5-positive DM patients.\u003c/p\u003e\u003cp\u003eLactic dehydrogenase represents a pivotal redox enzyme catalyzing pyruvate-to-lactate conversion. LDH is abundantly distributed in tissue of heart, liver, skeletal muscle, and lungs. When cells were damaged or ruptured, enhanced permeability facilitates LDH release into systemic circulation, elevating serum concentrations. Consequently, LDH serves as a significant tissue injury biomarker. Currently, LDH detection finds widespread application in myocardial infarction [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], liver injury [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and tumors [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Recent investigations have validated LDH's crucial role in pulmonary injury evaluation, with LDH levels closely correlating with acute respiratory distress syndrome prognosis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Nevertheless, LDH research regarding anti-MDA5-positive DM-associated interstitial lung disease remains limited. This manuscript retrospectively analysed 168 anti-MDA5-positive DM patients from the department of Rheumatology and Immunology at the Second Affiliated Hospital of Chongqing Medical University, explored the relationship between LDH and ILD so as to provide assistance for clinical guidance.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eFrom September 2015 to July 2025, 168 anti-MDA5-positive DM patients with ILD were hospitalized at the Second Affiliated Hospital of Chongqing Medical University. Patients comorbid with cardiac disease, hepatitis, skeletal muscle and myocardial involvement, pulmonary infections, and malignancies were excluded. Controls comprised health examination subjects at the same institution. In accordance with the Helsinki Declaration, all patients or relatives provided informed consent for participation and data publication. The ethics committee of the Second Affiliated Hospital of Chongqing Medical University approved this study.\u003c/p\u003e\u003cp\u003eLDH levels were quantified utilizing the lactic acid substrate methodology. Anti-MDA5 and anti-Ro-52 antibodies were tested using an OMRMUN assay kits (EUROIMMUN, Beijing, China). Serum ferritin were measured by chemiluminescence method using an Access Ferritin kit (Beckman Coulter, CA, USA).\u003c/p\u003e\u003cp\u003eGrouping: (1) LDH levels were evaluated by comparing 168 patients with anti-MDA5-positive DM before treatment in the control group. (2) High-resolution pulmonary computed tomography was performed in 168 patients with anti-MDA5-positive DM before and after treatment to assess the relationship between LDH and ILD. Based on radiological findings, patients were dichotomized: Group 1 (n\u0026thinsp;=\u0026thinsp;116): showed reduction or no significant changes in pulmonary lesions after treatment; Group 2 (n\u0026thinsp;=\u0026thinsp;52): exhibited newly emerged infiltrative shadows in the lungs on post-treatment imaging, defined as disease progression, excluding factors such as infection, pulmonary embolism, or heart failure [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. All CT evaluations were conducted by an experienced radiologist and espiratory specialist. (3) The 168 anti-MDA5-positive DM patients were stratified according to anti-Ro-52 antibody status, ferritin concentrations, and prognostic outcomes to examine LDH variations.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eAll analyses utilized SPSS 19.0 (IBM, Armonk, NY, USA). Normally distributed data were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, while non-normal distribution data were expressed as median and interquartile range. Mann-Whitney test were used to compare two groups. Wilcoxon test was used to compare the difference before and after treatment. Multiple comparisons were assessed by Kruskal-Wallis test. Values of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e1. Baseline Information\u003c/p\u003e\u003cp\u003eThe normal group encompassed 160 individuals (52 males, 108 females; male:female ratio 1:2.07; mean age 51.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6 years). A total of 168 anti-MDA5-positive DM patients, including 57 male and 111 female patients (male:female ratio 1:1.95; mean age 51.7\u0026thinsp;\u0026plusmn;\u0026thinsp;13.0 years). The LDH level was 143.5\u0026thinsp;\u0026plusmn;\u0026thinsp;30.2 U/L in the control group and 319 [250.2, 394] U/L in patients with anti-MDA5-positive DM before treatment, which was significantly elevated versus controls (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e2. The Relationship between LDH and Anti-Ro52 antibody\u003c/p\u003e\u003cp\u003e168 anti-MDA5-positive DM patients were dichotomized based on anti-Ro-52 antibody status. Results demonstrated: (1) Among the 111 patients with anti-Ro-52 antibody, the LDH level before treatment was 336 [(267, 403)] U/L. In contrast, among the 57 patients without anti-Ro-52 antibody, the LDH level before treatment was 299.6\u0026thinsp;\u0026plusmn;\u0026thinsp;107.7 U/L. A statistically significant difference was observed between the two groups, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01. (2) The LDH level of patients with positive anti-Ro-52 antibodies was 279 [193, 482] U/L after treatment, which was not significantly different from that before treatment (p\u0026thinsp;=\u0026thinsp;0.45). (3) The LDH level of patients without anti-Ro-52 antibodies was 203 [156, 776] U/L after treatment, which was significantly reduced compare to that before treatment (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of LDH levels in patients with anti-MDA5-positive DM with or without anti-Ro-52 antibodies before and after treatment\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnti-Ro-52 antibodies positive\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;111\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAnti-Ro-52 antibodies negative\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;57\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBefore treatment (U/L )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e336 [(267, 403)]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e299.6\u0026thinsp;\u0026plusmn;\u0026thinsp;107.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAfter\u003c/p\u003e\u003cp\u003etreatment (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e279 [(193, 482)]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e203 [(156, 776)]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e3. Relationship between LDH and serum ferritin\u003c/p\u003e\u003cp\u003e168 anti-MDA5-positive DM patients were categorized into three groups based on their ferritin levels. Group 1: serum ferritin\u0026lt;500ng/ml, (n\u0026thinsp;=\u0026thinsp;69), Group 2: 500ng/ml\u0026thinsp;\u0026le;\u0026thinsp;serum ferritin\u0026thinsp;\u0026lt;\u0026thinsp;1000ng/ml, (n\u0026thinsp;=\u0026thinsp;39), Group 3: 1000ng/ml\u0026thinsp;\u0026le;\u0026thinsp;serum ferritin\u0026thinsp;\u0026le;\u0026thinsp;1500ng/ml, (n\u0026thinsp;=\u0026thinsp;60). LDH level of patients before treatment in Group 1 was 278.2\u0026thinsp;\u0026plusmn;\u0026thinsp;84.6 U/L, significantly lower than that of patients in Groups 2 and 3 (Group 2: 340.4\u0026thinsp;\u0026plusmn;\u0026thinsp;82.9 U/L; Group 3: 382.5 [(301.3, 492.5)] U/L; respectively, p\u0026lt;0.01) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). After treatment, patients in Group 1 exhibited an LDH level of 193 [(158, 232)] U/L, which was significantly lower than that before treatment, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). The LDH level of patients in Group 2 after treatment was 234 [(186, 318)] U/L, markedly diminished compared to that before treatment, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). The LDH level of patients in Group 3 after treatment was 435.5 [(285, 577)] U/L, and the difference was not statistically significant compared with that before treatment, p\u0026thinsp;=\u0026thinsp;0.06 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e4. Relationship between LDH and ILD\u003c/p\u003e\u003cp\u003eTo elucidate LDH-ILD correlations before and after treatment, we divided 168 anti-MDA5-positive DM patients into two groups. Group 1, encompassing patients with improved or stabilized interstitial lung disease after treatment (n\u0026thinsp;=\u0026thinsp;115), and Group 2, comprising patients with deteriorated interstitial lung disease after treatment (n\u0026thinsp;=\u0026thinsp;53). In group 1, the LDH level of patients significantly decreased after treatment (before treatment: 297 [(242, 392)] U/L vs. after treatment: 201 [(174, 244)] U/L, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). Conversely, Group 2 demonstrated marked LDH elevation relative to baseline when interstitial lung disease deteriorated (before treatment: 342 [(279.5, 431.5)] U/L vs. after treatment: 512 [(395, 664)] U/L, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e5. Relationship between LDH and Prognosis\u003c/p\u003e\u003cp\u003e168 anti-MDA5-positive DM patients were categorized into a survival group (n\u0026thinsp;=\u0026thinsp;126) and a deceased group (n\u0026thinsp;=\u0026thinsp;42) based on their prognosis. (1) The LDH level before treatment in the survival group was 299.5 [(241.5, 392.3)] U/L, which was significantly lower than that in the deceased group (345.0 [(298.8, 472.0)] U/L, p\u0026thinsp;=\u0026thinsp;0.02). (2) After treatment, the LDH level in the survival group decreased to 203.5 [(174.8, 259.3)] U/L, which was significantly lower than that before treatment (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). (3) In the deceased group, the LDH level after treatment increased to 534.5 [(444.3, 666.5)] U/L, which was significantly higher than than that before treatment (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of LDH levels before and after treatment in patients with anti-MDA5-positive DM based on prognosis\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurvival group\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;126\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDeceased group\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;42\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBefore treatment (U/L )\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e299.5 [(241.5, 392.3)]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e345.0 [(298.8, 472.0)]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAfter\u003c/p\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003cp\u003e(U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e203.5 [(174.8, 259.3)]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e534.5 [(444.3, 666.5)]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAnti-MDA5-positive DM patients developing RP-ILD frequently manifest poor prognosis and elevated mortality rates, commanding escalating clinical attention. However, lung lesion assessments in anti-MDA5-positive DM remain relatively scarce with inherent constraints, such as radiation exposure caused by repeat chest CT scan in a short period of time, critical patients couldn't complete pulmonary function assessments adequately; and KL-6 testing practicality diminishes owing to economic constraints and temporal limitations. Consequently, identifying straightforward, innocuous, and efficacious biomarkers for evaluating ILD severity in anti-MDA5-positive DM patients assumes paramount significance. This investigation concentrated on analyzing LDH-ILD correlations in anti-MDA5-positive DM patients, endeavoring to furnish innovative clinical assessment methodologies.\u003c/p\u003e\u003cp\u003eOur findings demonstrated that the LDH levels in anti-MDA5-positive DM patients withILD before treatment were markedly elevated compared with those in control group, indicating that LDH is an important indicator that shouldn\u0026rsquo;t be ignored. Subsequently, we explored LDH correlations with anti-MDA5-positive DM comprehensively.\u003c/p\u003e\u003cp\u003eFirstly, extensive research has validated the pivotal role of anti-Ro-52 antibodies in inflammatory myopathies. Patients with anti-Ro-52 antibodies positive were more likely to develop rapidly progressive interstitial lung disease [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], subcutaneous and mediastinal emphysema [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and pharyngeal lesions [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Our study revealed that the LDH level before treatment was significantly elevated in patients with anti-Ro-52 antibodies than in those without anti-Ro-52 antibodies, confirming LDH-anti-Ro-52 antibodies associations in anti-MDA5-positive DM patients. Furthermore, no significant differences were found in the LDH level of patients positive for anti-Ro-52 antibodies before and after treatment, whereas the level of LDH in patients negative for anti-Ro-52 antibodies decreased significantly after treatment. This suggested anti-Ro-52 antibodies modulate therapeutic responsiveness, potentially attributable to more severe interstitial lung disease in anti-Ro-52-positive patients.\u003c/p\u003e\u003cp\u003eSecondly, serum ferritin is also an important evaluation indicator for anti-MDA5-positive DM. Takahisa et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] suggested that anti-MDA5-positive DM represents macrophage activation occurring in the lungs, distinguished by pronounced ferritin elevation. Through ferritin level stratification, we discerned that LDH levels in anti-MDA5-positive DM patients exhibited concordance with ferritin levels, showing a direct correlation between inflammatory magnitude and LDH elevation. Additionally, We found that under different inflammatory states, the difference of LDH levels of anti-MDA5 positive DM patients before and after treatment were also observed. Patients with serum ferritin\u0026thinsp;\u0026lt;\u0026thinsp;500 ng/ml and 500\u0026ndash;1000 ng/ml demonstrated significant post-treatment LDH attenuation versus baseline, signifying a better treatment response in mild-to-moderate inflammatory states. Conversely, when serum ferritin was between 1000 and 1500 ng/ml, no significant difference was found in LDH levels before and after treatment, indicating glucocorticoid and immunosuppressants have no improvement effect on LDH in severe inflammatory conditions. This finding bears profound clinical implications, underscoring the imperative for rheumatologists to judiciously modulate inflammatory burden in anti-MDA5-positive DM patients, thereby attenuating disease activity and improving the prognosis.\u003c/p\u003e\u003cp\u003eGiven anti-MDA5-positive DM's predominant lung manifestations, we prioritized LDH-ILD correlational analysis. Our data indicated that LDH levels diminish relative to baseline when ILD lesions were improved or stabilized post-treatment. Conversely, progressive ILD deterioration and intensified pulmonary injury precipitate substantial tissue LDH efflux into systemic circulation, markedly elevating serum concentrations versus pretreatment values. These observations establish positive correlation between LDH levels and ILD severity in anti-MDA5-positive DM patients. On the one hand, extracellular LDH functions as a damage-associated molecular pattern, promoting the release of inflammatory factors and exacerbating pulmonary inflammation. On the other hand, LDH's fundamental physiological role is to catalyze pyruvic acid into lactic acid. A high concentration of lactic acid in tissues can activate TGF-β, inducing myofibroblast differentiation and thus accelerating the pulmonary fibrosis process [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Our study confirmed that LDH was a simple yet effective biomarker to evaluate the changes in ILD in patients with anti-MDA5-positive DM.\u003c/p\u003e\u003cp\u003eFinally, regarding prognosis, the LDH levels were substantially elevated before treatment in the deceased group than in the survival group. After treatment, LDH levels in the deceased group escalated further, while exhibiting marked amelioration in the survival group, indicating LDH\u0026rsquo;s prognostic significance in anti-MDA5-positive DM. Analogous findings [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] in COVID-19 patients characterized by acute lung injury, it was found that non survivors had significantly higher levels of LDH than survivors. As a result, LDH was regarded as an important indicator for evaluating patients' respiratory function and predicting their prognosis. Combined with the above findings and our study, it was strongly confirmed that the pivotal role of LDH in lung lesions assessment in anti-MDA5-positive DM patients.\u003c/p\u003e\u003cp\u003eSeveral limitations warrant acknowledgement. Firstly, our study exclusively examined LDH\u0026rsquo;s relationship with anti-MDA5-positive DM, precluding characterization of other inflammatory myopathy types, such as antisynthetase syndrome. Secondly, mechanistic exploration remains superficial, requiring deeper investigation. Lastly, single-center clinical data necessitate multicenter validation with expanded sample sizes.\u003c/p\u003e\u003cp\u003eIn conclusion, this study elucidated LDH\u0026rsquo;s associations with serological markers, lung interstitial lesions, and prognosis in anti-MDA5-positive DM patients, furnishing clinically relevant insights and establishing groundwork for subsequent research.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflict of interest: There is no conflict of interest of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure statement:\u0026nbsp;\u003c/strong\u003eThere is no potential conflicts of interest of each author and this manuscript is approved by all authors for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003eAll data relevant to the study are included in the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003eI would like to thank my wife Dan Wang and my baby daughter Yuti Huang. It\u0026apos;s your endless love that makes me fearless.\u003c/p\u003e\n\u003cp\u003eAuthors consent: This manuscript was approved by all of the authors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSato S, Hirakata M, Kuwana M \u003cem\u003eet al\u003c/em\u003e.: Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. \u003cem\u003eArthritis Rheum\u003c/em\u003e 2005;52(5):1571-6. https://doi.org/10.1002/art.21023.\u003c/li\u003e\n\u003cli\u003eSato S, Hoshino K, Satoh T \u003cem\u003eet al\u003c/em\u003e.: RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease. \u003cem\u003eArthritis Rheum \u003c/em\u003e2009;60(7):2193-200. https://doi.org/10.1002/art.24621.\u003c/li\u003e\n\u003cli\u003eYang Y, Li Y, Yuan W \u003cem\u003eet al\u003c/em\u003e.: Risk factors for mortality in anti-MDA5 antibody-positive dermatomyositis with interstitial lung disease: a systematic review and meta-analysis. Front Immunol. 2025;16:1628748. https://doi: 10.3389/fimmu.2025.1628748. \u003c/li\u003e\n\u003cli\u003eLi H, Zou R, Xin H \u003cem\u003eet al\u003c/em\u003e.: Mortality Risk Prediction in Patients With Antimelanoma Differentiation-Associated, Gene 5 Antibody-Positive, Dermatomyositis-Associated Interstitial Lung Disease: Algorithm Development and Validation. J Med Internet Res. 2025;27:e62836. https://doi: 10.2196/62836. \u003c/li\u003e\n\u003cli\u003eYe Y, Fu Q, Wang R \u003cem\u003eet al\u003c/em\u003e.: Serum KL-6 level is a prognostic marker in patients with anti-MDA5 antibody-positive dermatomyositis associated with interstitial lung disease. J Clin Lab Anal. 2019;33(8):e22978. https://doi: 10.1002/jcla.22978.\u003c/li\u003e\n\u003cli\u003eWROBLEWSKI F, RUEGSEGGER P, LADUE JS. Serum lactic dehydrogenase activity in acute transmural myocardial infarction. Science. 1956;123(3208):1122-3. https://doi: 10.1126/science.123.3208.1122.\u003c/li\u003e\n\u003cli\u003eCassidy WM, Reynolds TB. Serum lactic dehydrogenase in the differential diagnosis of acute hepatocellular injury. J Clin Gastroenterol. 1994;19(2):118-21. https://doi: 10.1097/00004836-199409000-00008.\u003c/li\u003e\n\u003cli\u003eGallo M, Sapio L, Spina A \u003cem\u003eet al\u003c/em\u003e.: Lactic dehydrogenase and cancer: an overview. Front Biosci (Landmark Ed). 2015;20(8):1234-49. https://doi: 10.2741/4368.\u003c/li\u003e\n\u003cli\u003eZhang F, Zhang M, Niu Z \u003cem\u003eet al\u003c/em\u003e.: Prognostic value of lactic dehydrogenase-to-albumin ratio in critically ill patients with acute respiratory distress syndrome: a retrospective cohort study. J Thorac Dis. 2024;16(1):81-90. https://doi: 10.21037/jtd-23-1238.\u003c/li\u003e\n\u003cli\u003eRaghu G, Collard HR, Egan JJ \u003cem\u003eet al\u003c/em\u003e.: ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788-824. https://doi: 10.1164/rccm.2009-040GL.\u003c/li\u003e\n\u003cli\u003eChen Y, Chen YF, Chiu LC \u003cem\u003eet al\u003c/em\u003e.: Coexistence of anti-melanoma differentiation-associated protein 5 and anti-Ro52 antibodies in patients with idiopathic inflammatory myopathy: a retrospective cohort study. Clin Rheumatol. 2025. https://doi: 10.1007/s10067-025-07562-1. Epub ahead of print.\u003c/li\u003e\n\u003cli\u003eHuang W, Chen D, Ren F \u003cem\u003eet al\u003c/em\u003e.: The clinical characteristics of subcutaneous and mediastinal emphysema in anti-melanoma differentiation-associated 5 positive dermatomyositis associated with interstitial lung disease. Clin Exp Rheumatol. 2024;42(2):262-268. https://doi: 10.55563/clinexprheumatol/84kd56.\u003c/li\u003e\n\u003cli\u003eHuang W, Ren F, Deng D \u003cem\u003eet al\u003c/em\u003e.: The clinical characteristics of pharyngeal and laryngeal lesions in anti-MDA5-positive dermatomyositis patients. Clin Exp Rheumatol. 2025;43(2):276-281. https://doi: 10.55563/clinexprheumatol/t0478a.\u003c/li\u003e\n\u003cli\u003eGono T, Sato S, Kawaguchi Y \u003cem\u003eet al\u003c/em\u003e.: Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology (Oxford). 2012;51(9):1563-70. https://doi: 10.1093/rheumatology/kes102. \u003c/li\u003e\n\u003cli\u003eKottmann RM, Kulkarni AA, Smolnycki KA \u003cem\u003eet al\u003c/em\u003e.: Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-\u0026beta;. Am J Respir Crit Care Med. 2012;186(8):740-51. https://doi: 10.1164/rccm.201201-0084OC.\u003c/li\u003e\n\u003cli\u003eLi G, Xu F, Yin X \u003cem\u003eet al\u003c/em\u003e.: Lactic dehydrogenase-lymphocyte ratio for predicting prognosis of severe COVID-19. Medicine (Baltimore). 2021;100(4):e24441. https://doi: 10.1097/MD.0000000000024441.\u003c/li\u003e\n\u003cli\u003eGupta GS. The Lactate and the Lactate Dehydrogenase in Inflammatory Diseases and Major Risk Factors in COVID-19 Patients. Inflammation. 2022;45(6):2091-2123. https://doi: 10.1007/s10753-022-01680-7.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"anti-MDA5-positive DM, lactic dehydrogenase, interstitial lung disease, anti-Ro-52 antibodies, serum ferritin","lastPublishedDoi":"10.21203/rs.3.rs-7551189/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7551189/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThis study aimed to investigate the relationship between lactic dehydrogenase (LDH) and anti-melanoma differentiation-associated gene 5 antibodies-positive dermatomyositis (anti-MDA5-positive DM) complicated by interstitial lung disease (ILD).\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e\u003cp\u003e168 anti-MDA5-positive DM patients with ILD underwent comprehensive evaluation, including LDH, anti-Ro-52 antibodies, serum ferritin determination, and lung high-resolution CT.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe level of LDH were significantly elevated in anti-MDA5-positive DM patients compared with control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Anti-Ro-52-positive patients demonstrated significantly higher LDH levels compared to anti-Ro-52-negative patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Patients with elevated serum ferritin exhibited markedly increased LDH levels compared with those with lower serum ferritin (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). After treatment, LDH levels significantly increased in patients with ILD deterioration (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), whereas LDH decreased in patients with ILD amelioration or stabilization (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The LDH levels were significantly elevated in the death group compared to the survival group before treatment (p\u0026thinsp;=\u0026thinsp;0.02).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003e1. The LDH levels were affected by anti-Ro-52 antibodies and serum ferritin. 2. The ILD severity of anti-MDA5-positive DM patients positively correlated with LDH, suggesting that LDH might serve as an effective assessment indicator to evaluate the changes in ILD in these patients. 3. Elevated LDH levels were a crucial indicator of poor prognosis in anti-MDA5-positive DM patients, warranting close attention from rheumatologists.\u003c/p\u003e","manuscriptTitle":"Evaluating Value of Lactic Dehydrogenase in Anti-MDA5-positive Dermatomyositis Associated with Interstitial Lung Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-26 06:59:40","doi":"10.21203/rs.3.rs-7551189/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c15c5ace-e7ae-4d06-9864-659f44989965","owner":[],"postedDate":"September 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-26T06:59:42+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-26 06:59:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7551189","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7551189","identity":"rs-7551189","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}