Research in Review: Novel Biomarkers for Atopic Dermatitis Identified in Newborns

Atopic dermatitis (AD), commonly referred to as eczema, is a complex condition that afflicts nearly 30% of children worldwide.(1) It is especially common in infants and is correlated with the development of food allergies, allergic rhinitis and asthma – also known as the atopic march. Early identification and proactive treatment to prevent or reduce AD development could result in significant improvements in quality of life and potentially reduce the risk of atopic march in patients.

Understanding the gene-gene and gene-environment interactions that influence inflammation and skin flare-ups is particularly challenging. Heterogeneity in the disease presentation is influenced by multiple factors – from dysregulated cytokines and immune mediator activation to host-microbe interactions and aberrant epidermal barrier function.(2) As such, a ‘one-size-fits-all’ therapeutic to treat or prevent AD is not likely to be possible. Currently, most AD patients rely on various topical corticosteroid treatments during flare-ups to encourage skin renewal and repair the damaged epithelial layer. More recently, approved topical immune-modulating agents, such as crisaborole (Eucrisa®) or injectable biologics, such as dupilumab (Dupixent®), are showing greater success in certain patients. Discovering key disease-related biomarkers that can predict disease development or differentiate various clinical presentations of the disease are critical to developing targeted therapeutics for disease subpopulations and could ultimately be useful diagnostic tools in clinical practice. In recent years, these advances have led to a surge in at least 70 new topical and systemic compounds in clinical development.(3) With continued research into the molecular mechanisms of AD, precision medicine approaches offer a renewed hope for disease management and prevention.

Recent research published in the Journal of Allergy and Clinical Immunology has identified several novel early skin biomarkers that could be used to predict early onset of AD in newborns before any clinical signs are present.(4) Using non-invasive skin tape biospecimen collection from two-month-old newborns, with and without a family history of AD, researchers were able to identify several predictive biomarkers in the stratum corneum (SC) of infants that went on to develop AD. These included decreased levels of key protein-bound ceramides that are crucial for SC maturation and epidermal barrier formation, upregulation of IL-13, and the presence of a combination of type 2 cytokines and lipid biomarkers. These various markers combined with familial history of atopic diseases were considered strong predictors of future AD development, with an odds ratio between 20 and 54. As the study was limited to infants of Asian ethnicity, replication of these results in other ethnicities would strengthen the predictive factor of this data. These results could help guide precision medicine approaches clinically in the future based on the biomarker profile of the patient. Theoretically, this could involve screening newborns for various markers and then delivering emollients containing certain ceramides or biologics targeting the Th2-skewed immune response to preemptively halt the onset or treat AD.

The discoveries in this study were made using non-invasive skin tape biospecimen collection in 111 babies, of which 74 were identified as being at risk for AD. This method uses medical adhesive tape to pull off inflamed skin cells in a quick and painless process, replacing the need for invasive biopsies in research. These skin tapes were analyzed through mass spectrometry for a wide panel of lipid molecules and by cytokine immunoassays to gain insight into the mechanisms involved in skin barrier function and the immune response. Skin taping can be a valuable tool in biomarker discovery across various skin-related autoimmune diseases, providing a snapshot of the patient’s epidermal profile. This non-invasive method is particularly advantageous because it is extremely safe to use, even on newborn skin, and can provide a wealth of information in research and clinical applications. Ultimately, uncovering the molecular features of various skin diseases can help us understand disease etiology and identify new therapeutic pathways.

Here at Sanguine, we offer skin taping biospecimen collection as well as customizable laboratory processing and testing to aid in biomarker research and scientific discovery. We are pioneers in patient-centric mobile study recruitment and prospective biospecimen procurement, bringing research participation to the comfort of patients’ homes to achieve rapid enrollment and high study retention rates. Our database of >60,000 willing research participants across the United States gives us access to many disease populations, including various autoimmune diseases, such as AD, psoriasis, or cutaneous lupus erythematosus patients. Contact us to learn more about our innovative approach to biospecimen collection and research and how we can help set your study up for success.

 

 

References

1. Abuabara K, Yu AM, Okhovat JP, Allen IE, Langan SM. The prevalence of atopic dermatitis beyond childhood: A systematic review and meta-analysis of longitudinal studies. Allergy. 2018 Mar;73(3):696–704.
2. Luger T, Amagai M, Dreno B, Dagnelie MA, Liao W, Kabashima K, et al. Atopic dermatitis: Role of the skin barrier, environment, microbiome, and therapeutic agents. J Dermatol Sci. 2021 Jun;102(3):142–57.
3. Bieber T. Atopic dermatitis: an expanding therapeutic pipeline for a complex disease. Nat Rev Drug Discov. 2022 Jan;21(1):21–40.
4. Berdyshev E, Kim J, Kim BE, Goleva E, Lyubchenko T, Bronova I, et al. Stratum corneum lipid and cytokine biomarkers at age 2 months predict the future onset of atopic dermatitis. Journal of Allergy and Clinical Immunology. 2023 Feb;S0091674923002270.