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Stratum corneum markers of innate and T helper cell-related immunity and their relation to the disease severity in Croatian patients with atopic dermatitis

Jurakic Toncic, R; Jakasa, I; Sun, Y; Hurault, G; Ljubojevic Hadzavdic, S; Tanaka, RJ; Pavicic, B; ... Marinovic, B; + view all (2021) Stratum corneum markers of innate and T helper cell-related immunity and their relation to the disease severity in Croatian patients with atopic dermatitis. Journal of the European Academy of Dermatology and Venereology , 35 (5) pp. 1186-1196. 10.1111/jdv.17132.

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Abstract

BACKGROUND: Atopic dermatitis (AD) presents with the wide spectrum of clinical phenotypes within and between various populations. Recent study showed low frequency of filaggrin loss-of-function (FLG LOF) mutations in Croatian AD patients. At present, there are no data on biomarkers of immune response in Croatian AD patients that might be useful in the selection and monitoring of novel immune therapies. OBJECTIVES: To investigate levels of cytokines of various signature in the stratum corneum (SC) collected from lesional and non-lesional skin of AD patients and healthy controls, and to evaluate their relationship with the severity of disease and skin barrier function. METHODS: SC samples were collected from 100 adult patients with moderate to severe AD and 50 healthy controls. The levels of 21 cytokines were measured by multiplex immunoassay. We conducted machine learning analysis to assess whether a small number of cytokine measurements can discriminate between healthy controls and AD patients and can predict AD severity (SCORAD). RESULTS: The SC levels of thirteen cytokines representing innate immunity, Th-1, Th-2 and Th-17/22 immune response showed significant differences between healthy and AD skin. Our analysis demonstrated that as few as three cytokines measured in lesional skin can discriminate healthy controls and AD with an accuracy of 99%, and that the predictive models for SCORAD did not achieve a high accuracy. Cytokine levels were highly correlated with the levels of filaggrin degradation products and skin barrier function. CONCLUSIONS: Stratum corneum analysis revealed aberrant levels of cytokines representing innate immunity, Th-1, Th-2 and Th-17/22 mediated immune response in Croatian AD patients. Increased Th-2 cytokines, and their strong association with natural moisturizing factor (NMF) can explain low NMF levels despite of low frequency of FLG LOF mutations in Croatian population. Predictive models for SCORAD identified cytokines associated with SCORAD but warrants further investigation.

Type: Article
Title: Stratum corneum markers of innate and T helper cell-related immunity and their relation to the disease severity in Croatian patients with atopic dermatitis
Location: England
DOI: 10.1111/jdv.17132
Publisher version: https://doi.org/10.1111/jdv.17132
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: adaptive immunity, feature selection, atopic dermatitis, biomarkers, classification, cytokines, innate immunity, non-invasive, regression
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
URI: https://discovery.ucl.ac.uk/id/eprint/10119964
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