作者
Helen He,Ester Del Duca,Aisleen Diaz,Hyun Je Kim,Jesús Gay-Mimbrera,Ning Zhang,Jianni Wu,Jessica Beaziz,Yeriel Estrada,James G. Krueger,Ana B. Pavel,Juan Ruano,Emma Guttman‐Yassky
摘要
Background
Molecular studies in atopic dermatitis (AD) are largely restricted to patients with moderate-to-severe disease. Objective
Our aim was to evaluate skin and blood abnormalities in mild, moderate, and severe AD. Methods
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. Results
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 TH2 cell–, TH22 cell–, TH1 cell–, and TH17 cell–related mediators demonstrated incremental elevations with increasing disease severity, in both lesional and nonlesional skin. Whereas the levels of the TH2 (IL13, CCL17, and CCL26) and TH22 (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 TH1 cell (IFNG, CXCL9, and CXCL10) and TH17 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 TH1 cell–, TH2 cell–, and TH17 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. Conclusion
Mild and limited AD show high levels of TH2/TH22 cell activation that is primarily localized to skin lesions and lacks the systemic inflammation of moderate and severe disease.