Transcriptomic Analysis of Allergic Patch Test Reactions in Non‐Atopic Patients: A Comparative Study Across Multiple Allergens
David Pesqué, Evelyn Andrades, Pau Berenguer‐Molins, Júlia Perera‐Bel, Miquel Clarós, Marta Bódalo‐Torruella, Mònica González‐Farré, Fernando Gallardo, Ramon M. Pujol, Ana M. Giménez‐Arnau
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).