Skin microdialysis detects distinct immunologic patterns in chronic inflammatory skin diseases - 04/09/24

Doi : 10.1016/j.jaci.2024.06.024

Moritz Maximilian Hollstein, MD ^a,^⁎ , Stephan Traidl, MD ^b, Anne Heetfeld, MD ^a, Susann Forkel, MD ^a, Andreas Leha, PhD ^c, Natalia Alkon, PhD ^d, Jannik Ruwisch, MD ^e, Christof Lenz, PhD ^f,^g, Michael Peter Schön, MD ^a, Martin Schmelz, MD ^h, Patrick Brunner, MD, MSc ⁱ, Martin Steinhoff, MD, PhD ^j, Timo Buhl, MD ^a
^a Department of Dermatology, Venereology and Allergology, University Medical Centre Göttingen (UMG), Göttingen, Germany
^b Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany
^c Department of Medical Statistics, UMG, Göttingen, Germany
^d Department of Dermatology, Medical University of Vienna, Vienna, Austria
^e Clinic for Respiratory Medicine, Hannover Medical School, Hannover, Germany
^f Department of Clinical Chemistry, UMG, Göttingen, Germany
^g Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
^h Department of Experimental Pain Research, MCTN, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
ⁱ Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY
^j Department of Dermatology and Venereology, Hamad Medical Corporation, Doha, Qatar

^∗Corresponding author: Moritz Hollstein, MD, University Medical Center Göttingen, Department of Dermatology, Venereology and Allergology, Robert Koch Str 40, 37075 Göttingen, Germany.University Medical Center GöttingenDepartment of DermatologyVenereology and AllergologyRobert Koch Str 40Göttingen37075Germany

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 04 September 2024

Graphical abstract

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Abstract

Background

Insight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data.

Objective

We characterized lesional and nonlesional skin of inflammatory skin diseases using skin microdialysis.

Methods

Skin microdialysis samples from patients with atopic dermatitis (AD, n = 6), psoriasis vulgaris (PSO, n = 7), or prurigo nodularis (PN, n = 6), as well as healthy controls (n = 7), were subjected to proteomic and multiplex cytokine analysis. Single-cell RNA sequencing of skin biopsy specimens was used to identify the cellular origin of cytokines.

Results

Among the top 20 enriched Gene Ontology (GO; geneontology.org) annotations, nicotinamide adenine dinucleotide metabolic process, regulation of secretion by cell, and pyruvate metabolic process were elevated in microdialysates from lesional AD skin compared with both nonlesional skin and controls. The top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG; kegg) pathways in these 3 groups overlapped almost completely. In contrast, nonlesional skin from patients with PSO or PN and control skin showed no overlap with lesional skin in this KEGG pathway analysis. Lesional skin from patients with PSO, but not AD or PN, showed significantly elevated protein levels of MCP-1 compared with nonlesional skin. IL-8 was elevated in lesional versus nonlesional AD and PSO skin, whereas IL-12p40 and IL-22 were higher only in lesional PSO skin. Integrated single-cell RNA sequencing data revealed identical cellular sources of these cytokines in AD, PSO, and PN.

Conclusion

On the basis of microdialysates, the proteomic data of lesional PSO and PN skin, but not lesional AD skin, differed significantly from those of nonlesional skin. IL-8, IL-22, MCP-1, and IL-12p40 might be suitable markers for minimally invasive molecular profiling.

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Key words : Microdialysis, pruritus, atopic dermatitis, psoriasis vulgaris

Abbreviations used : AD, CCL, CXCL, EASI, FWHM, GO, KEGG, LC-MS/MS, MCP, MIP, MS, MS/MS, PASI, PCA, PN, PSO, scRNA-Seq, SWATH, TSLP