Characterization of High and Low IFNG-Expressing Subgroups in Atopic Dermatitis.

Autor: Wasserer S; Department of Dermatology and Allergy, Technical University of Munich, 80802 Munich, Germany., Jargosch M; Department of Dermatology and Allergy, Technical University of Munich, 80802 Munich, Germany.; Center of Allergy & Environment (ZAUM), Technical University of Munich, Helmholtz Center Munich, 80802 Munich, Germany., Mayer KE; Department of Dermatology and Allergy, Technical University of Munich, 80802 Munich, Germany., Eigemann J; Department of Dermatology and Allergy, Technical University of Munich, 80802 Munich, Germany.; Center of Allergy & Environment (ZAUM), Technical University of Munich, Helmholtz Center Munich, 80802 Munich, Germany., Raunegger T; Department of Dermatology and Allergy, Technical University of Munich, 80802 Munich, Germany., Aydin G; Department of Dermatology and Allergy, Technical University of Munich, 80802 Munich, Germany., Eyerich S; Center of Allergy & Environment (ZAUM), Technical University of Munich, Helmholtz Center Munich, 80802 Munich, Germany., Biedermann T; Department of Dermatology and Allergy, Technical University of Munich, 80802 Munich, Germany., Eyerich K; Department of Dermatology and Allergy, Medical Center, University of Freiburg, 79104 Freiburg, Germany., Lauffer F; Department of Dermatology and Allergy, Technical University of Munich, 80802 Munich, Germany.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Jun 03; Vol. 25 (11). Date of Electronic Publication: 2024 Jun 03.
DOI: 10.3390/ijms25116158
Abstrakt: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, with an increasing number of targeted therapies available. While biologics to treat AD exclusively target the key cytokines of type 2 immunity, Janus kinase inhibitors target a broad variety of cytokines, including IFN-γ. To better stratify patients for optimal treatment outcomes, the identification and characterization of subgroups, especially with regard to their IFNG expression, is of great relevance, as the role of IFNG in AD has not yet been fully clarified. This study aims to define AD subgroups based on their lesional IFNG expression and to characterize them based on their gene expression, T cell secretome and clinical attributes. RNA from the lesional and non-lesional biopsies of 48 AD patients was analyzed by RNA sequencing. Based on IFNG gene expression and the release of IFN-γ by lesional T cells, this cohort was categorized into three IFNG groups (high, medium, and low) using unsupervised clustering. The low IFNG group showed features of extrinsic AD with a higher prevalence of atopic comorbidities and impaired epidermal lipid synthesis. In contrast, patients in the high IFNG group had a higher average age and an activation of additional pro-inflammatory pathways. On the cellular level, higher amounts of M1 macrophages and natural killer cell signaling were detected in the high IFNG group compared to the low IFNG group by a deconvolution algorithm. However, both groups shared a common dupilumab response gene signature, indicating that type 2 immunity is the dominant immune shift in both subgroups. In summary, high and low IFNG subgroups correspond to intrinsic and extrinsic AD classifications and might be considered in the future for evaluating therapeutic efficacy or non-responders.
Competing Interests: Sophia Wasserer has received honoraria and travel support from Novartis, Sanofi-Regeneron, Janssen and Lilly. Felix Lauffer has been an advisor and/or received speaker’s honoraria and/or received grants and/or participated in clinical trials for the following companies: Abbvie, Almirall, Amgen, Biogen, Boehringer Inglheim, Bristol-Myers-Squibb, Janssen, LEO Pharma, Pfizer, Lilly, Novartis, Roche, Sanofi, UCB, Union Therapeutics and Biogen. Kristine E. Mayer has received travel support from Novartis. Kilian Eyerich has received grants and honoraria and has served as a speaker, investigator, consultant and/or advisor for AbbVie, Almirall, Boehringer Ingelheim, BMS, Celgene, Hexal, Galapagos, Galderma, Janssen, Eli Lilly, Pfizer, Novartis, Sanofi and UCB Pharma. Tilo Biedermann gave advice to and received honoraria for talks or research grants from the following companies: Abbvie, Alk-Abelló, Boehringer-Ingelheim, Celgene-BMS, Leo Pharma, Lilly Deutschland GmbH, Novartis, Sanofi-Genzyme, Regeneron and Viatris. No specific conflicts of interest were declared in relation to this article.
Databáze: MEDLINE
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