Screening of Metabolic Reprogramming-Related Diagnostic Biomarkers and Analysis of Immune Heterogeneity in Atopic Dermatitis Based on Multi-Cohort Validation.

BACKGROUND: Atopic dermatitis (AD), often called eczema, is a long-lasting skin condition that causes severe itching and distress for many people. While we know it involves the immune system and the skin barrier, we still do not fully understand how changes in how skin cells process energy affect the disease. We wanted to look into these energy processes to find better ways to help people living with eczema and see how their experiences differ from people with other skin conditions like psoriasis. METHODS: We gathered and analyzed genetic data shared by patients and healthy volunteers across multiple study groups. Instead of looking at thousands of genes at once, we focused on groups of genes that metabolic reprogramming-related. We used computer models to see if specific genes could help identify people with eczema. We also studied how these genes relate to the immune cells present in the skin, and used this information to see if we could group patients into different molecular types. RESULTS: We discovered two specific genes, called RRM2 and HMMR, that are highly active in people living with eczema. These two genes successfully helped us distinguish people with eczema from both healthy individuals and people living with psoriasis. Patients with higher activity in these genes also showed a stronger presence of active immune cells in their skin. By looking at these patterns, we found that people with eczema generally fall into one of two distinct groups, each having its own unique immune features. CONCLUSION: This study identifies RRM2 and HMMR as promising candidate biomarkers associated with metabolic reprogramming in AD and reveals distinct immune heterogeneity and potential molecular subtypes, offering a preliminary framework for further exploration of subtype-guided strategies in AD. If further validated, these findings may assist in differential diagnosis and guide subtype‑specific therapeutic strategies for patients with AD.