Transcriptomic Analysis of Allergic Patch Test Reactions in Non-Atopic Patients: A Comparative Study Across Multiple Allergens.

Abstract

BACKGROUND Immune mechanisms underlying elicitation in allergic contact dermatitis (ACD) have yet to be fully elucidated. Previous studies have shown a double-faceted nature of ACD with both common biomarkers among different allergens and allergen-specific imprinting, albeit with discordance in terms of relevant pathways involved. Several factors, including co-existing atopic dermatitis, may influence immune reactions. We aim to characterize molecular signatures and their immune mechanisms of different relevant allergens (nickel, 2-hydroxyethylmethacrylate [2-HEMA], methylisothiazolinone [MIT], formaldehyde) in strong and extreme positive (2/3+) patch test reactions of patients without atopic dermatitis. METHODS A transcriptomic analysis of 40 skin biopsies of ACD reactions (11 nickel, 10 MIT, 10 2-HEMA, 9 formaldehyde) and 19 controls (petrolatum-occluded skin) was performed using RNA sequencing. Differentially expressed genes (DEG) were assessed, and enriched functional pathways were obtained with an over-representation analysis for allergens. RESULTS ACD molecular profiling revealed a strong, common imprinting of DEG among allergens versus controls (n = 814), with further partially shared DEG among allergens (n = 664) and allergen-specific DEG (n = 430). The most relevant shared pathways were associated with immune adaptive and innate responses. All allergens exhibited mixed effector immune responses, mainly type 1 and 3 immunity, and, to a lesser extent, type 2 immunity. Furthermore, partially shared and unique DEG were associated with further inflammatory pathways, particularly for nickel and 2-HEMA. CONCLUSIONS This study confirms shared ACD imprinting among different allergens and shared pathways' predominant role in ACD elicitation in patients without atopic dermatitis, alongside allergen-specific immune processes and mixed effector responses (type 1, 3 and 2).