Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
Department of Dermatology, Reina Sofía University Hospital, Córdoba, Spain.
J Allergy Clin Immunol. 2021 Apr;147(4):1369-1380. doi: 10.1016/j.jaci.2020.08.041. Epub 2020 Oct 1.
Molecular studies in atopic dermatitis (AD) are largely restricted to patients with moderate-to-severe disease.
Our aim was to evaluate skin and blood abnormalities in mild, moderate, and severe AD.
Skin and blood samples were obtained from 61 patients with AD (20 with mild or limited disease, 17 with moderate disease, and 24 with severe disease) and 20 healthy subjects. Immune and barrier markers were measured in lesional, nonlesional, and healthy skin by quantitative real-time PCR and immunohistochemistry, and in blood by using the OLINK proteomic assay.
Cellular markers of epidermal hyperplasia and T-cell/dendritic cell infiltration were increased in AD tissues of all patients in all severity groups versus in those of controls, whereas downstream T2 cell-, T22 cell-, T1 cell-, and T17 cell-related mediators demonstrated incremental elevations with increasing disease severity, in both lesional and nonlesional skin. Whereas the levels of the T2 (IL13, CCL17, and CCL26) and T22 (IL-22) cytokines were significantly elevated in both AD lesional and nonlesional skin of all patients regardless of the severity of their disease, patients with mild or limited AD showed increases in their levels of T1 cell (IFNG, CXCL9, and CXCL10) and T17 cell (IL-17A, CCL20, and CXCL1) markers in lesional but not nonlesional skin. Regulatory T-cell-related mediators (IL-10 and FOXP3) were comparably upregulated in all groups, without displaying the severity-based gradient in other immune axes. Unsupervised clustering aligned samples along a severity spectrum, where nonlesional mild or limited AD skin clustered with the samples from healthy controls. Furthermore, whereas the blood profiles of patients with moderate and severe AD showed gradual increases in the levels of T1 cell-, T2 cell-, and T17 cell-related and atherosclerosis and/or cardiovascular risk (CCL7, FGF21, and IGFBP1) proteins, the blood profiles of patients with mild or limited AD lacked significant differences from those of the controls.
Mild and limited AD show high levels of T2/T22 cell activation that is primarily localized to skin lesions and lacks the systemic inflammation of moderate and severe disease.
特应性皮炎（AD）的分子研究主要局限于中重度疾病患者。
我们旨在评估轻度、中度和重度 AD 的皮肤和血液异常。
从 61 例 AD 患者（20 例轻度或局限性疾病，17 例中度疾病，24 例重度疾病）和 20 例健康受试者中获取皮肤和血液样本。通过实时定量 PCR 和免疫组化在病变、非病变和健康皮肤中测量免疫和屏障标志物，并通过 OLINK 蛋白质组学分析在血液中测量。
所有严重程度组的 AD 患者的皮肤组织中表皮增生和 T 细胞/树突状细胞浸润的细胞标志物均高于对照组，而下游 T2 细胞、T22 细胞、T1 细胞和 T17 细胞相关介质的表达水平随着疾病严重程度的增加而逐渐升高，病变和非病变皮肤均如此。尽管所有患者的 AD 病变和非病变皮肤中 T2（IL13、CCL17 和 CCL26）和 T22（IL-22）细胞因子的水平均显著升高，但轻度或局限性 AD 患者的 T1 细胞（IFNG、CXCL9 和 CXCL10）和 T17 细胞（IL-17A、CCL20 和 CXCL1）标志物的水平仅在病变皮肤中升高，而非病变皮肤中则没有升高。调节性 T 细胞相关介质（IL-10 和 FOXP3）在所有组中均被上调，但在其他免疫轴上并未显示出与严重程度相关的梯度。无监督聚类根据严重程度将样本排列在一个连续谱上，其中非病变的轻度或局限性 AD 皮肤与健康对照组的样本聚类在一起。此外，尽管中度和重度 AD 患者的血液特征显示 T1 细胞、T2 细胞和 T17 细胞相关蛋白以及动脉粥样硬化和/或心血管风险（CCL7、FGF21 和 IGFBP1）水平逐渐升高，但轻度或局限性 AD 患者的血液特征与对照组相比没有显著差异。
轻度和局限性 AD 表现出高水平的 T2/T22 细胞激活，主要局限于皮肤病变，缺乏中重度疾病的全身炎症。
