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.