Analysis: 31 Inflammatory Proteins Impacted by Atopic Dermatitis

An analysis of blood samples identified 31 differently expressed proteins (DEPs) that were either significantly up-regulated or down-regulated in participants with atopic dermatitis versus healthy controls. The collection of observed inflammatory proteins impacted by the presence of atopic dermatitis may provide clinicians a better understanding of the common skin disease’s complex mechanisms—as well as clearer targets for direct pharmacological intervention.

A team of investigators from Korea conducted a 1:1 analysis of blood samples from a cohort of atopic dermatitis patients, versus healthy controls, in order to observe the spectrum of proteins associated with dermatitis inflammation, as well as the link between systemic biomarkers and disease severity.

“Atopic dermatitis is a chronic inflammatory cutaneous disorder, that emerges from intricate interplays among genetic predisposition, immune dysregulation, environmental factors, and compromised skin barrier,” the team wrote. “Understanding the inflammatory pathway in AD is important due to its fundamental role in the pathogenesis of AD.”

Led by Yu Ri Woo, of the department of dermatology at Incheon St. Mary’s Hospital at The Catholic University of Korea College of Medicine, investigators enrolled 48-adult cohorts of those living with atopic dermatitis and health controls for their assessment. Patients were aged 18 – 90 years old, and were excluded if they were pregnant or breastfeeding, or had been currently or previously diagnosed with other inflammatory skin diseases, autoimmune disorders, malignancy or acquired immunodeficiency syndrome. The team assessed atopic dermatitis disease severity via Eczema Area Severity Index (EASI) to establish mild (<16), moderate (16 – 23), and severe (≥23) diseases.

Investigators generated blood proteomics data via the Olink platform, using an inflammation panel to assess factors of atopic dermatitis.

Participant demographics across the 2 cohorts were fairly similar; mean age was approximately 32 years old, and two-thirds of participants were male. Among the atopic dermatitis cohort, a majority (n = 26 [57.8%]) of patients had severe EASI scores and eosinophil percent was 11.43%. A combined 10 patients were on either cyclosporine or methotrexate for their condition.

The Olink proteomics platform assessed 92 inflammatory proteins. Of them, 31 DEPs were identified as significantly affected in patients with atopic dermatitis versus the healthy control cohort. A majority were up-regulated (n = 29); only the IL-20RA and FGF5 proteins were significantly down-regulated versus the healthy control results.

The 5 most significantly impacted that which showed a positive correlation with atopic dermatitis severity were:

• MCP-3 (R, 0.687; P <.001)
• IL-18 (R, 0.571; P <.001)
• MCP-4 (R, 0.567; P <.001)
• TNFRSF9 (R, 0.558; P <.001)
• IL-17C (R, 0.436; P = .002)

Investigators additionally observed positive correlations between atopic dermatitis patient age and 3 DEPs:

• CXCL10 (R, 0.592; P <.001)
• IL-10 (R, 0.561; P = .001)
• INF-gamma (R, 0.463; P = .009)

Woo and colleagues additionally observed positive correlation between serum eosinophil counts, total immunoglobulin E (IgE) levels and a handful of other proteins among patients with atopic dermatitis.

“Eosinophils, essential in atopic dermatitis-associated allergic inflammation, show increased production, recruitment, and delayed apoptosis,” investigators noted. “The correlation between CD5, IL-18, IL-13, TNFRSF9, and total IgE levels in AD suggests a complex interplay of immune responses.”

Thought the trial emphasized blood proteomics, the team believes that skin proteomic analysis as a follow-up may provided them a “more localized view” of inflammation and its interaction in the skin. Though this analysis was limited by a small sample size of a homogenous population, Woo and colleagues concluded their research may help provide a progression into clinically-applicable intervention strategies for atopic dermatitis.

“These DEPs correlate with clinical severity, suggesting their potential as biomarkers for disease progression,” they wrote. “This paves the way for targeted therapies and personalized medicine in atopic dermatitis, improving diagnostic and therapeutic strategies.”

References

1. ^{Woo YR, Moon JH, Shin HY, Bang YJ, et al. Systemic Inflammatory Proteomic Biomarkers in Atopic Dermatitis: Exploring Potential Indicators for Disease Severity. J Korean Med Sci. 2024 Aug 12;39(31):e223. English. Published online Jul 11, 2024.
   https://doi.org/10.3346/jkms.2024.39.e223}
2. ^{Simon D, Braathen LR, Simon HU. Eosinophils and atopic dermatitis. Allergy 2004;59(6):561–570.}