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Maintz, L.* ; Welchowski, T.* ; Herrmann, N.* ; Brauer, J.* ; Traidl-Hoffmann, C. ; Havenith, R.* ; Müller, S.* ; Rhyner, C.* ; Dreher, A.* ; Schmid, M.* ; Bieber, T.*

IL-13, periostin and dipeptidyl-peptidase-4 reveal endotype-phenotype associations in atopic dermatitis.

Allergy 78, 1554-1569 (2023)

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BACKGROUND: The heterogeneous (endo)phenotypes of atopic dermatitis (AD) require precision medicine. Currently, systemic therapy is recommended to patients with an Eczema Area and Severity Index (EASI)≥16. Previous studies have demonstrated an improved treatment response to the anti-interleukin (IL)-13 antibody tralokinumab in AD subgroups with elevated levels of the IL-13-related biomarkers dipeptidyl-peptidase (DPP)-4 and periostin. METHODS: Herein, 373 AD patients aged≥12 years were stratified by IL-13^high , periostin^high and DPP-4^high endotypes using cross-sectional data from the ProRaD cohort Bonn. "High" was defined as >80^th quantile of 47 non-atopic controls. We analyzed endotype-phenotype associations using machine-learning gradient boosting compared to logistic regression. RESULTS: AD severity and eosinophils correlated with IL-13 and periostin levels. Correlations of IL-13 with EASI were stronger in patients with increased (rs=0.482) than with normal (rs=0.342) periostin levels. We identified eosinophilia>6% and an EASI range of 5.5-17 dependent on the biomarker combination to be associated with increasing probabilities of biomarker^high endotypes. Also patients with mild-to-low-moderate severity (EASI<16) featured increased biomarkers (IL-13^high : 41%, periostin^high : 48.4%, DPP-4^high : 22.3%). Herthoge sign (adjusted Odds Ratio (aOR)=1.89, 95% Confidence Interval (CI) [1.14-3.14]) and maternal allergic rhinitis (aOR=2.79-4.47) increased the probability of an IL-13^high -endotype, "dirty neck" (aOR=2.83 [1.32-6.07]), orbital darkening (aOR=2.43 [1.08-5.50]), keratosis pilaris (aOR=2.21 [1.1-4.42]) and perleche (aOR=3.44 [1.72-6.86]) of a DPP-4^high -endotype. CONCLUSIONS: A substantial proportion of patients with EASI<16 featured high biomarker levels suggesting systemic impact of skin inflammation already below the current cut-off for systemic therapy. Our findings facilitate the identification of patients with distinct endotypes potentially linked to response to IL-13-targeted therapy.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Atopic Dermatitis ; Biomarker ; Endotype ; Interleukin-13 ; Tralokinumab; Double-blind; Alopecia-areata; Serum Periostin; Moderate; Placebo; Activation; Asthma; Adolescents; Biomarkers; Psoriasis

ISSN (print) / ISBN 0105-4538

e-ISSN 1398-9995

Journal Allergy

Quellenangaben Volume: 78, Issue: 6, Pages: 1554-1569

Publisher Wiley

Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Environmental Medicine (IEM)

Grants LEO Pharma Research Foundation
Christine Kuehne-Center for Allergy Research and Education