Unique molecular signatures typify skin inflammation induced by chemical allergens and irritants

Allergy. 2021 Dec;76(12):3697-3712. doi: 10.1111/all.14989. Epub 2021 Jul 14.

Abstract

Background: Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic.

Methods: To characterize the molecular signatures of chemical-induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants.

Results: A clear segregation was observed between allergen- and irritant-induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T-cell responses. Our results also confirmed that: (a) unique pathways characterize allergen- and irritant-induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine-learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation.

Conclusion: These results highlight the value of molecular profiling of chemical-induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis.

Keywords: allergic contact dermatitis; biomarker; chemical allergens; chemical irritants; transcriptomic profiling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens
  • Dermatitis, Allergic Contact* / diagnosis
  • Dermatitis, Allergic Contact* / etiology
  • Dermatitis, Irritant* / etiology
  • Dermatitis, Irritant* / genetics
  • Humans
  • Inflammation
  • Irritants / adverse effects
  • Patch Tests

Substances

  • Allergens
  • Irritants