Overview
Study Overview Atopic dermatitis (AD), commonly known as eczema, is a chronic inflammatory skin condition characterized by intense itching and skin barrier damage. While researchers know that the immune system is overactive in AD, it is difficult to measure the exact level of "damage" or "inflammation" happening deep within the skin using only a physical exam.
The Purpose of This Study This study investigates a specific "danger signal" called circulating cell-free DNA (cfDNA). When skin cells are damaged or die due to inflammation, they release tiny fragments of DNA into the bloodstream. We believe these fragments might act as a trigger for the immune system, worsening the disease.
What the Study Involves
Researchers will collect blood samples and small skin biopsies from patients with AD and healthy volunteers. The study aims to:
Compare the levels of cfDNA in the blood of AD patients versus healthy individuals.
Determine if higher levels of cfDNA correlate with more severe skin symptoms (measured by scores like SCORAD and EASI).
Examine how immune cells in the skin (macrophages) respond to these DNA fragments through a specific biological switch called the STING pathway.
Potential Impact By understanding this "damage-signal" loop, this research may lead to new ways for doctors to monitor AD severity through simple blood tests and could identify new targets for future anti-inflammatory treatments.
Description
Scientific RationaleAtopic dermatitis (AD) is primarily driven by Type 2 (Th2) immune responses; however, the role of innate immune sensing of damage-associated molecular patterns (DAMPs) in maintaining chronic inflammation is less defined. Cell-free DNA (cfDNA) has emerged as a potent DAMP in various autoimmune conditions. This study explores the hypothesis that cfDNA released during epidermal injury and inflammatory cell turnover in AD serves as a ligand for the cyclic GMP-AMP synthase (cGAS) - Stimulator of Interferon Genes (STING) pathway within the skin microenvironment.Study ObjectivesQuantification of Systemic DAMPs: To quantify plasma cfDNA concentrations in a cohort of AD patients (n=40) compared to age- and sex-matched healthy controls (n=40) using fluorometric assays. Tissue-Level Mechanism: To characterize the local immune landscape via immunofluorescence (IF) staining of skin biopsies. The study focuses on the infiltration density of CD68+ macrophages and the expression/co-localization of STING protein within these cells.MethodologyClinical Assessment: Patients undergo standardized dermatological evaluation to determine disease severity.Bio-sampling: Peripheral blood is collected for baseline hematology and cfDNA isolation. For a subset of patients, 4mm punch biopsies are taken from active lesional skin. Data Analysis: Cross-sectional analysis will be used to determine the diagnostic value of cfDNA and its ability to stratify disease severity (Moderate vs. Severe AD). Immunohistochemical quantification will be used to verify the activation of the STING pathway in situ.
Eligibility
Inclusion Criteria:Patients aged older than 18 with a confirmed diagnosis of AD and visible skin lesions.
Exclusion Criteria:Patients who have received systemic immunosuppressants, systemic corticosteroids, or biological agents (e.g., Dupilumab) within the past 4 weeks, or topical treatments within the past 2 weeks, to avoid interference with inflammatory markers.
