Atopic Dermatitis Endotypes Based on Allergen Sensitization, Reactivity to Staphylococcus aureus Antigens, and Underlying Systemic Inflammation.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease with significant local and systemic inflammation and barrier disruption. AD is associated with increased risk of allergen sensitization and skin colonization by Staphylococcus aureus. The heterogeneity of AD is unknown, and its complexity suggests its subdivision into several endotypes. OBJECTIVE: To evaluate allergy-driven endotypic differences in patients with AD and identify proteomic signatures to distinguish between inflammatory responses. To perform proteomic profiling of allergen sensitivity, antibody levels to S aureus antigens, and circulating inflammatory mediators to characterize AD subsets in 76 subjects with moderate to severe AD and 39 healthy controls (HCs). METHODS: Sera were collected from 76 subjects with moderate to severe AD and 39 HCs with no history of skin disease. Serum was tested for levels of total serum immunoglobulin E (IgE) and allergen-specific IgE using a panel of 119 allergens as well as IgE antibodies against S aureus antigens, and was profiled for more than 1100 proteins by SOMAscan to detect differential expression of inflammatory mediators. RESULTS: Total serum IgE levels were significantly (P < .001) elevated in subjects with AD versus controls. A greater percentage of subjects with AD were allergic compared with HCs, and patients with AD tested positive to a greater number of allergens than did HCs. IgE was upregulated across 4 allergen subsets (food, perennial, seasonal, and mixed), and each allergen subset was associated with a distinct inflammatory signature marked by a specific suite of upregulated proteins. Finally, IgE antibodies against S aureus toxic shock syndrome toxin-1 were significantly upregulated in subjects with seasonal allergy (P = .0430) and perennial allergy (P = .00032). CONCLUSIONS: Overall, this study addresses the heterogeneity of AD by characterizing subsets of AD on the basis of allergen sensitization. It also demonstrates the differential systemic inflammation and S aureus-specific antibody responses associated with the allergenic endotypes. These unique proteomic signatures may be valuable for precise disease characterization and subsequent personalized treatment.