Jurakic Toncic R, Jakasa I, Sun Y, Hurault G, Ljubojevic Hadzavdic S, Tanaka R J, Pavicic B, Balic A, Zuzul K, Petkovic M, Kezic S, Marinovic B
Department of Dermatology and Venereology, School of Medicine in Zagreb, University Hospital Center, Zagreb, Croatia.
Laboratory for Analytical Chemistry, Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia.
J Eur Acad Dermatol Venereol. 2021 May;35(5):1186-1196. doi: 10.1111/jdv.17132. Epub 2021 Feb 13.
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.
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.
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).
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.
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.
特应性皮炎（AD）在不同人群内部和之间呈现出广泛的临床表型。最近的研究表明，克罗地亚AD患者中丝聚蛋白功能丧失（FLG LOF）突变的频率较低。目前，尚无关于克罗地亚AD患者免疫反应生物标志物的数据，这些标志物可能有助于新型免疫疗法的选择和监测。
研究从AD患者和健康对照的皮损和非皮损皮肤收集的角质层（SC）中各种特征性细胞因子的水平，并评估它们与疾病严重程度和皮肤屏障功能的关系。
从100例中重度AD成年患者和50例健康对照中收集SC样本。通过多重免疫测定法测量21种细胞因子的水平。我们进行了机器学习分析，以评估少量细胞因子测量能否区分健康对照和AD患者，并能否预测AD严重程度（SCORAD）。
代表先天免疫、Th-1、Th-2和Th-17/22免疫反应的13种细胞因子的SC水平在健康皮肤和AD皮肤之间存在显著差异。我们的分析表明，在皮损皮肤中测量的低至三种细胞因子就能以99%的准确率区分健康对照和AD患者，并且SCORAD预测模型未达到高精度。细胞因子水平与丝聚蛋白降解产物水平和皮肤屏障功能高度相关。
角质层分析揭示了克罗地亚AD患者中代表先天免疫、Th-1、Th-2和Th-17/22介导的免疫反应的细胞因子水平异常。尽管克罗地亚人群中FLG LOF突变频率较低，但Th-2细胞因子增加及其与天然保湿因子（NMF）的强关联可以解释NMF水平较低的原因。SCORAD预测模型确定了与SCORAD相关的细胞因子，但仍需进一步研究。
