Integrated analysis of dermatomyositis reveals heterogeneous immune infiltration and interstitial lung disease-associated endotype
Abstract Background Dermatomyositis (DM) is an autoimmune disease with a high rate of disability and mortality especially in DM with concurrent interstitial lung disease (DM-ILD). Little is known about inflammatory signature and heterogeneous endotypes of DM. Objective We aimed to illustrate the sys...
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| Language: | English |
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BMC
2025-02-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-025-03494-y |
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| author | Xinzhi Xu Tianwen Qiu Kexin Sun Xue Han Junxia Huang Xiuyuan Wang Jianchao Ge Ji Yang |
| author_facet | Xinzhi Xu Tianwen Qiu Kexin Sun Xue Han Junxia Huang Xiuyuan Wang Jianchao Ge Ji Yang |
| author_sort | Xinzhi Xu |
| collection | DOAJ |
| description | Abstract Background Dermatomyositis (DM) is an autoimmune disease with a high rate of disability and mortality especially in DM with concurrent interstitial lung disease (DM-ILD). Little is known about inflammatory signature and heterogeneous endotypes of DM. Objective We aimed to illustrate the systemic inflammatory signature of DM and define an ILD-associated endotype. Methods Olink proteomic analysis was performed on serum samples obtained from DM patients (n = 32), DM patients with ILD (n = 16), and healthy controls (n = 19). Transcriptomic data from skin samples was utilized to assess immune infiltration and investigate the correlation between protein and mRNA levels of biomarkers. Additionally, the prognostic value and clinical significance of identified biomarkers were validated through follow-up studies of DM patients and immunofluorescence analysis of skin tissues. Results Proteomic data revealed the inflammatory signature of DM, with GO and KEGG enrichment analyses identifying chemotaxis-related pathways. Transcriptomic analysis of skin samples indicated upregulated inflammatory responses and M1 macrophage infiltration in DM. Two chemokines, CXCL10 and CXCL11, were identified as highly associated with immune infiltration and DM progression. Conclusions Our data suggest that serum CXCL10 and CXCL11 reflect the inflammatory burden of DM. The identified biomarkers hold promise for determining an ILD-associated endotype and predicting clinical outcomes, thereby paving the way for timely management of DM and prevention of complications. |
| format | Article |
| id | doaj-art-8b202c91d2c94fc29edd37bc424deaa5 |
| institution | Kabale University |
| issn | 1478-6362 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj-art-8b202c91d2c94fc29edd37bc424deaa52025-02-09T12:48:44ZengBMCArthritis Research & Therapy1478-63622025-02-0127111110.1186/s13075-025-03494-yIntegrated analysis of dermatomyositis reveals heterogeneous immune infiltration and interstitial lung disease-associated endotypeXinzhi Xu0Tianwen Qiu1Kexin Sun2Xue Han3Junxia Huang4Xiuyuan Wang5Jianchao Ge6Ji Yang7Department of Dermatology, Zhongshan Hospital of Fudan UniversityDepartment of Dermatology, School of Medicine, East Hospital, Shanghai Tongji UniversityDepartment of Dermatology, Zhongshan Hospital of Fudan UniversityDepartment of Dermatology, Zhongshan Hospital of Fudan UniversityDepartment of Dermatology, Zhongshan Hospital of Fudan UniversityDepartment of Dermatology, Zhongshan Hospital of Fudan UniversityNinth People’ S Hospital, Shanghai Jiaotong University School of MedicineDepartment of Dermatology, Zhongshan Hospital of Fudan UniversityAbstract Background Dermatomyositis (DM) is an autoimmune disease with a high rate of disability and mortality especially in DM with concurrent interstitial lung disease (DM-ILD). Little is known about inflammatory signature and heterogeneous endotypes of DM. Objective We aimed to illustrate the systemic inflammatory signature of DM and define an ILD-associated endotype. Methods Olink proteomic analysis was performed on serum samples obtained from DM patients (n = 32), DM patients with ILD (n = 16), and healthy controls (n = 19). Transcriptomic data from skin samples was utilized to assess immune infiltration and investigate the correlation between protein and mRNA levels of biomarkers. Additionally, the prognostic value and clinical significance of identified biomarkers were validated through follow-up studies of DM patients and immunofluorescence analysis of skin tissues. Results Proteomic data revealed the inflammatory signature of DM, with GO and KEGG enrichment analyses identifying chemotaxis-related pathways. Transcriptomic analysis of skin samples indicated upregulated inflammatory responses and M1 macrophage infiltration in DM. Two chemokines, CXCL10 and CXCL11, were identified as highly associated with immune infiltration and DM progression. Conclusions Our data suggest that serum CXCL10 and CXCL11 reflect the inflammatory burden of DM. The identified biomarkers hold promise for determining an ILD-associated endotype and predicting clinical outcomes, thereby paving the way for timely management of DM and prevention of complications.https://doi.org/10.1186/s13075-025-03494-yDermatomyositisInterstitial lung diseaseProteomicImmune infiltrationEndotype |
| spellingShingle | Xinzhi Xu Tianwen Qiu Kexin Sun Xue Han Junxia Huang Xiuyuan Wang Jianchao Ge Ji Yang Integrated analysis of dermatomyositis reveals heterogeneous immune infiltration and interstitial lung disease-associated endotype Arthritis Research & Therapy Dermatomyositis Interstitial lung disease Proteomic Immune infiltration Endotype |
| title | Integrated analysis of dermatomyositis reveals heterogeneous immune infiltration and interstitial lung disease-associated endotype |
| title_full | Integrated analysis of dermatomyositis reveals heterogeneous immune infiltration and interstitial lung disease-associated endotype |
| title_fullStr | Integrated analysis of dermatomyositis reveals heterogeneous immune infiltration and interstitial lung disease-associated endotype |
| title_full_unstemmed | Integrated analysis of dermatomyositis reveals heterogeneous immune infiltration and interstitial lung disease-associated endotype |
| title_short | Integrated analysis of dermatomyositis reveals heterogeneous immune infiltration and interstitial lung disease-associated endotype |
| title_sort | integrated analysis of dermatomyositis reveals heterogeneous immune infiltration and interstitial lung disease associated endotype |
| topic | Dermatomyositis Interstitial lung disease Proteomic Immune infiltration Endotype |
| url | https://doi.org/10.1186/s13075-025-03494-y |
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