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Background <p>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.</p> Objective <p>We aimed to illustrate the systemic inflammatory signature of DM and define an ILD-associated endotype.</p> Methods <p>Olink proteomic analysis was performed on serum samples obtained from DM patients (<i>n</i> = 32), DM patients with ILD (<i>n</i> = 16), and healthy controls (<i>n</i> = 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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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Integrated analysis of dermatomyositis reveals heterogeneous immune infiltration and interstitial lung disease-associated endotype

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月8日

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  • Xinzhi Xu,
  • Tianwen Qiu,
  • Kexin Sun,
  • Xue Han,
  • Junxia Huang,
  • Xiuyuan Wang,
  • Jianchao Ge,
  • Ji Yang

摘要

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.