Study Highlights Top 5 Inflammatory Biomarkers, Relationship with Atopic Dermatitis Severity

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The differentially expressed proteins (DEPs) known as TNFRSF9, IL-18, MCP-4, MCP-3, and IL-17C are the top 5 associated with severity of atopic dermatitis, according to new findings, suggesting their possible use as biomarkers for disease progression monitoring.¹

These new findings highlighted a total of 29 DEPs which were significantly up-regulated and 2 which were substantially down-regulated in atopic dermatitis versus healthy controls. The data were the conclusions of new research authored by investigators such as Yu Ri Woo, from the department of dermatology at the Catholic University of Korea’s Incheon St. Mary’s Hospital in Seoul.

“By analyzing systemic inflammatory biomarkers, this study aims to uncover insights into the systemic inflammatory response in (atopic dermatitis),” Woo et al. wrote. “It seeks to establish correlations between systemic biomarkers and disease severity, potentially leading to the development of diagnostic and prognostic tools, and improving patient management and therapeutics in (atopic dermatitis).”

Trial Design and Background

The investigators noted that while there had been prior exploration of individual markers in skin and blood, there was a general lack of comprehensive research covering both topics.² They further commented that such research had also not evaluated a large East Asian patient cohort.

Recruitment of 48 individuals with atopic dermatitis in addition to an equal set of healthy controls took place at Seoul National University Hospital and Eunpyeong St. Mary’s Hospital located in the Catholic University of Korea. These subjects’ prior diagnoses of atopic dermatitis had been made according to the diagnostic criteria for the condition in Korea.

Among those with the skin disorder included in the study, their severity of disease was evaluated specifically using the Eczema Area and Severity Index (EASI) scoring system. The research team noted that an EASI score under 16 suggested mild disease, a score between 16 - 23 suggested moderate disease, and 23 or higher suggested more severe cases.

Eligibility criteria for enrollment in the study included being between the ages of 18 - 90 years, without consideration of race as long as participants did not have a history of or current inflammatory skin condition, acquired immunodeficiency syndrome, autoimmune disorder, or cancer. They also were required by the team to not be pregnant or breastfeeding.

The investigators determined their healthy control subjects carefully with the aim of excluding those with atopic comorbidities. They gathered blood proteomics data of all participants through the Olink platform, looking specifically at the inflammation panel.

In heparin CPT tubes, blood samples were collected and then centrifuged at 1,800 g for 20 minutes at room temperature. The plasma samples resulting from this process were then stored at −80°C until the time of the investigators’ experiments.

Findings

Overall, the investigators identified a distinct set of proteins in their proteomic analysis which differentiated those with atopic dermatitis from healthy controls. They reported that 29 proteins were upregulated and 2 that were downregulated, with the former set of proteins including Th1 cytokines like IFN-gamma, IL-18, and IL-8; Th2 cytokines such as IL-13, IL-10, and TGF-alpha; and Th17 cytokines, such as IL-17C and IL-6.

The research team also noted that several proteins involved in inflammatory responses (EN-RAGE, TNFSF14, oncostatin M), cellular signaling and regulation (STAMBP, AXIN1, and 4E-BP1), metabolism (ADA), cell death (SIRT2, and CASP-8), tissue remodeling and angiogenesis (VEGFA, MMP-1, and HGF) were upregulated, as were several chemokines (MCP-4, MCP3, CXCL10, CCL4, CCL20, CXCL11, and CCL3).

In the team’s correlation analysis, IL-18, MCP-4, IL-17C, MCP-3, and TNFRSF9 were found to be the top 5 DEPs which had the most strong link to severity of atopic dermatitis. The positive correlation identified by the investigators with the skin disease’s severity highlights these DEPs potential as biomarkers.

“This study provides insights into the complex inflammatory profile of (atopic dermatitis) but acknowledges its limitations,” they wrote. “Future research should address these limitations to enhance understanding and translate findings into clinical applications. Our analysis identified 31 DEPs in (atopic dermatitis) patients compared to (healthy controls), revealing a complex interplay of cytokines and chemokines. These DEPs correlate with clinical severity, suggesting their potential as biomarkers for disease progression.”

References

1. ^{Woo YR, Moon JH, Shin HY, Bang YJ, Song S, Lee S, Lee DH, Kim HJ, Kim JE. Systemic Inflammatory Proteomic Biomarkers in Atopic Dermatitis: Exploring Potential Indicators for Disease Severity. J Korean Med Sci. 2024 Jul;39(31):e223. https://doi.org/10.3346/jkms.2024.39.e223.}
2. ^{Renert-Yuval Y, Thyssen JP, Bissonnette R, Bieber T, Kabashima K, Hijnen D, et al. Biomarkers in atopic dermatitis-a review on behalf of the International Eczema Council. J Allergy Clin Immunol 2021;147(4):1174–1190.e1.}