Molecular Diagnosis of Atopic Dermatitis by Transcriptome Profiling of Signature Genes
Principle Investigator: Tesfaye Mersha, PhD
Atopic dermatitis (AD) is a chronic relapsing eczematous skin disorder that affects up to 20 percent of the U.S. population, with treatment that costs U.S. taxpayers $3.8 billion annually. Nearly 80 percent of the children with AD develop asthma or allergic rhinitis later in life, underscoring its public health impact. AD is currently diagnosed using patient history and visual assessment of the skin as no specific laboratory test is available for clinical use.
The current treatment for AD involves topical application of moisturizers, corticosteroids or calcineurin inhibitors, or systemic cytokine-targeted therapies. However, both topical as well as systemic therapies require identification of target patients to choose suitable treatment options and to assess treatment benefits. Recent studies demonstrated that AD has a multifactorial etiology involving skin barrier and immune-related genes indicating the need for a comprehensive molecular profiling for patient-centric treatment. Using multiple independent transcriptomic datasets, we discovered a panel of 89 signature genes that discriminate AD from control skin biopsy samples with 98 percent predictive accuracy.
We plan to develop a skin-directed molecular profiling tool for AD under the following two specific aims: a) collect skin biopsy and tape strip samples derived from patients and controls; b) perform targeted RNA-sequencing (RNA-Seq) to validate our previously identified 89 AD-relevant gene signature panel and implement a Tagman qPCR-based assay to generate an “AD score.” The AD score is the sum of the degree of genes over/under expressed across the gene signature panel compared to the housekeeping genes used.
This diagnostic platform will use the expression levels of a signature gene panel, similar to the commercially available “EoGenius” platform for eosinophilic esophagitis (EoE) developed by Marc Rothenberg, MD, and his team. Our proposal has a high potential to drive significant change in clinical practice by using molecular profiling approaches to provide a new and robust diagnostic platform for patients with AD. Success in this project includes (1) the implementation of a minimally invasive skin sample collection method that can be easily performed at the point of clinical care and is well suited for pediatric AD patients, and (2) the development of RNA-Seq-based molecular profiling approach relevant to personalized care for children with AD. This technology can be potentially expanded to include transcriptomic signature panels for other skin diseases like psoriasis and contact dermatitis.