INTRODUCTION
Atopic dermatitis (AD) is a highly complex, heterogeneous, chronic inflammatory skin condition characterized by a pruritic, erythematous rash whose immune pathophysiology remains unclear. While AD has been shown to affect up to 25% of children and 3% of adults worldwide, incidence rates has been increasing 2- to 3-fold over the last several decades [1]. Although many pediatric cases are transient in nature, AD is often the first step of the atopic march and active disease throughout life with up to 75% of adults with AD reporting onset during childhood [2]. An early diagnosis of AD has been linked with the development of additional atopic comorbidities, such as allergic rhinitis, food allergy, and asthma [3]. This link may be the result of similar underlying mechanisms of disease development involving the circulating inflammatory immune milieu in AD patients since type 2 cytokines, barrier function proteins, and allergen-specific IgE responses have been implicated in both disease onset and persistence [4, 5].
The comorbid nature of AD, as well as its development in early childhood, makes it an attractive target for predictive studies of disease development highlighting the importance of characterizing these early stages of pathogenesis. The systemic nature of AD has only recently been explored within younger patients demonstrating the presence and persistence of cell populations that produce biomarkers like IL-22, IL-17a, and IFNγ, and strong correlations to cells capable of producing IL-13 were shown to increase from childhood to adulthood [6, 7]. Because AD is a complex disease involving multiple cell types, chemokines, and cytokines, further longitudinal studies identifying additional biomarkers and correlating them to disease manifestations are needed to truly characterize the complex underlying immune signals of AD pathogenesis that drive barrier disruption and atopy development. Therefore, using high-throughput and ultrasensitive protein quantitation methods, we evaluated 126 secreted proteins from the serum of 87 children diagnosed with AD in their first year of life and correlated levels of inflammatory proteins to disease progression over the course of this 5-year study.
Our findings provide further insight into the systemic inflammatory serum protein and cell population profile present in the circulation of pediatric AD patients. Previous studies utilizing this cohort of patients revealed correlations with AD to atopic and nonatopic eczema, food allergy, and asthma [8, 9]. Several biomarkers indicative of active type 2 immune responses were correlated with both progression of disease and cell phenotypes which have been linked to comorbidities associated with non-AD-like conditions such as childhood wheezing [10]. These correlations in early life demonstrate the potential for development of targeted therapeutics for younger patients with mild to moderate disease. In this manuscript, we highlight key insights into the pathology of AD, outlining the correlations with analytes previously identified in adult moderate to severe disease and their role in disease development even in this mild to moderate cohort of pediatric subjects.