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Published on: December 19, 2019
Skin barrier damage after exposure to paraphenylenediamine
Sanne S Meisser1, Can Altunbulakli2, Josefine Bandier3
1Research Centre for Hairdressers and Beauticians and the National Allergy Research Centre, Department of Dermatology and Allergy, University Hospital Gentofte, Hellerup, Switzerland; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Switzerland; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, and the Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
Background:
p-Phenylenediamine (PPD) is a strong contact allergen used in hair dye that is known to cause allergic contact dermatitis (ACD). Both private and occupational exposure to PPD is frequent, but the effect of PPD exposure in nonallergic occupationally exposed subjects is unknown.
Objective:
We sought to investigate the effects of PPD exposure on the skin of occupationally exposed subjects with and without clinical symptoms.
Methods:
Skin biopsy specimens were collected from 4 patients with mild and 5 patients with severe PPD-related ACD and 7 hairdressers without contact dermatitis on day 4 after patch testing with 1% PPD in petrolatum. RNA sequencing and transcriptomics analyses were performed and confirmed by using quantitative RT-PCR. Protein expression was analyzed in skin from 4 hairdressers and 1 patient with ACD by using immunofluorescence staining. Reconstructed human epidermis was used to test the effects of PPD in vitro.
Results:
RNA sequencing demonstrated downregulation of tight junction and stratum corneum proteins in the skin of patients with severe ACD after PPD exposure. Claudin-1 (CLDN-1), CLDN8, CLDN11, CXADR-like membrane protein (CLMP), occludin (OCLN), membrane-associated guanylate kinase inverted 1 (MAGI1), and MAGI2 mRNA expression was downregulated in patients with severe ACD. CLDN1 and CLMP expression were downregulated in nonresponding hairdressers and patients with mild ACD. Filaggrin 1 (FLG1), FLG2, and loricrin (LOR) expression were downregulated in patients with ACD. Confocal microscopic images showed downregulation of CLDN-1, FLG-1, and FLG-2 expression. In contrast, 3-dimensional skin cultures showed upregulation of FLG-1 in response to PPD but downregulation of FLG-2.
Conclusion:
PPD-exposed skin is associated with extensive transcriptomic changes, including downregulation of tight junction and stratum corneum proteins, even in the absence of clinical symptoms.
