J Korean Med Sci.  2024 Aug;39(31):e223. 10.3346/jkms.2024.39.e223.

Systemic Inflammatory Proteomic Biomarkers in Atopic Dermatitis: Exploring Potential Indicators for Disease Severity

• Woo YR
• Moon JH
• Shin HY
• Bang YJ
• Song S
• Lee S
• Lee DH
• Kim HJ
• Kim JE

• KMID: 2558524
• DOI: http://doi.org/10.3346/jkms.2024.39.e223

Abstract

Background
Atopic dermatitis (AD) is a chronic inflammatory cutaneous disorder, that emerges from intricate interplays among genetic predisposition, immune dysregulation, environmental factors, and compromised skin barrier. Understanding the inflammatory pathway in AD is important due to its fundamental role in the pathogenesis of AD. This study aimed to explore the diverse spectrum of proteins linked to the inflammation of AD and the relationship between systemic biomarkers and clinical severity in AD.
Methods
We examined the blood samples from 48 patients with AD and 48 healthy controls (HCs) using the Proximity Extension Assay (Olink). Differentially expressed proteins (DEPs) were identified and Pearson correlation analysis was conducted to determine systemic proteomic biomarkers associated with severity of AD.
Results
A total of 29 DEPs were significantly up-regulated and 2 DEPs were significantly down-regulated in AD compared with the HC. The MCP-4, IL-18, MCP-3, TNFRSF9, and IL-17C were the top 5 highest DEPs associated with the severity of AD.
Conclusion
Our study sheds light on the intricate network of inflammatory proteins in AD and their potential implications for disease severity. Our results indicate that these systemic inflammatory proteins could be valuable for assessing AD severity and enhancing our understanding of the disease's complexity and its potential management strategies.

Keyword

Atopic Dermatitis; Biomarker; Inflammation; Proteomics; Severity

Figure

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  Fig. 1 Serum molecular differences distinguishing AD patients from HCs. (A) A heatmap of 92 markers in the Inflammation panel among AD and HC. (B) Principal component analysis reveals molecular differences in the serum of AD compared to HCs.AD = atopic dermatitis, HC = healthy control.

• 

  Fig. 2 Inflammation-related protein expression differences between AD and HC. (A) A volcano plot displaying the expression landscape of 92 inflammation-related proteins, highlighting those significantly altered in AD compared to HC. (B) A bar graph showing log2 fold changes of all identified differentially expressed proteins meeting the criteria of [Log2FC] ≥ 0.5 and P < 0.05. (C) Heatmap of differentially expressed inflammation-related proteins between AD and HC.AD = atopic dermatitis, HC = healthy control, FC = fold change.

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  Fig. 3 GO enrichment analysis of DEPs. The GO enrichment analysis highlights the most relevant (A) biological process and (B) molecular function terms associated with the DEPs.GO = Gene Ontology, DEP = differentially expressed protein.

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  Fig. 4 Correlation between protein expression and clinical severity of AD. (A) Correlation matrix heatmap among 31 differentially expressed proteins and clinical severity measured by eczema area and severity index in AD patients. (B-F) Correlation analysis of the top 5 proteins most associated with clinical severity. The proteins significantly correlated with the clinical severity of AD were defined by a P value < 0.05 and a correlation coefficient > 0.4 or < −0.4.AD = atopic dermatitis.

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  Fig. 5 Correlation matrix heatmap of 31 differentially expressed proteins, age, eosinophils, and total IgE in atopic dermatitis patients.

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