Grieco Teresa, Paolino Giovanni, Moliterni Elisa, Chello Camilla, Sernicola Alvise, Egan Colin Gerard, Morelli Mariangela, Nannipieri Fabrizio, Battaglia Santina, Accoto Marina, Tirotta Erika, Trasciatti Silvia, Bonaretti Silvano, Pellacani Giovanni, Calvieri Stefano
Dermatology Clinic, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy.
Unit of Dermatology and Cosmetology, IRCCS University Vita-Salute San Raffaele, 20132 Milan, Italy.
Int J Mol Sci. 2024 Dec 30;26(1):211. doi: 10.3390/ijms26010211.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by proteins involved in skin barrier maintenance and vitamin D metabolism. Using an intra-patient design, this study compared protein expression in intra-lesional (IL) and peri-lesional (PL) skin biopsies from AD patients and examined associations between protein levels, vitamin D status, and clinical features. Forty-four biopsies from twenty-two AD patients were analyzed using antibody microarrays targeting twelve proteins. IL samples had significantly higher total protein levels than PL samples, with a mean difference of 77.7% ( < 0.001). Several proteins, including cathelicidin, cingulin, occludin, filaggrin, and the vitamin D receptor, were upregulated in IL samples. Patients with vitamin D levels below 30 ng/mL showed higher expression of CYP24A ( = 0.054), alpha-catenin ( = 0.043), and haptoglobin ( = 0.033). Increased EASI scores (≥16) were associated with elevated expression of CYP24A ( = 0.024), CYP27B ( = 0.044), filaggrin ( = 0.027), occludin ( = 0.049), and claudin-1 ( = 0.052). Multivariate regression analysis identified significant correlations between protein expression, skin prick test positivity, and low vitamin D levels. These findings suggest that proteins related to epithelial barrier function and vitamin D metabolism are highly upregulated in IL skin regions, offering potential therapeutic targets for improving both skin barrier function and overall disease severity in AD patients.
特应性皮炎（AD）是一种慢性炎症性皮肤病，受参与皮肤屏障维持和维生素D代谢的蛋白质影响。本研究采用患者自身对照设计，比较了AD患者皮损内（IL）和皮损周围（PL）皮肤活检组织中的蛋白质表达，并检测了蛋白质水平、维生素D状态与临床特征之间的关联。使用针对12种蛋白质的抗体微阵列分析了来自22例AD患者的44份活检组织。IL样本的总蛋白水平显著高于PL样本，平均差异为77.7%（<0.001）。包括cathelicidin、cingulin、occludin、丝聚合蛋白和维生素D受体在内的几种蛋白质在IL样本中上调。维生素D水平低于30 ng/mL的患者CYP24A（=0.054）、α-连环蛋白（=0.043）和触珠蛋白（=0.033）表达较高。湿疹面积及严重程度指数（EASI）评分增加（≥16）与CYP24A（=0.024）、CYP27B（=0.044）、丝聚合蛋白（=0.027）、occludin（=0.049）和claudin-1（=0.052）表达升高相关。多变量回归分析确定了蛋白质表达、皮肤点刺试验阳性和低维生素D水平之间的显著相关性。这些发现表明，与上皮屏障功能和维生素D代谢相关的蛋白质在IL皮肤区域高度上调，为改善AD患者的皮肤屏障功能和整体疾病严重程度提供了潜在的治疗靶点。
