Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York.
J Am Acad Dermatol. 2019 Aug;81(2):510-519. doi: 10.1016/j.jaad.2019.04.036. Epub 2019 Apr 19.
Despite increasing evidence that adults with long-standing atopic dermatitis (AD) have systemic inflammation, little is known about systemic inflammation in recent-onset early pediatric AD.
To analyze blood inflammatory proteins of early pediatric AD.
Using high-throughput proteomics (proximity extension assay), we assessed 257 inflammatory and cardiovascular risk proteins in the blood of 30 children with moderate to severe AD younger than 5 years of age (within 6 months of onset) compared with age-matched pediatric control individuals and adult patients with AD.
In pediatric AD blood, T helper (Th) type 2 (CCL13, CCL22) and Th17 (peptidase inhibitor-3/elafin) markers were increased, together with markers of tissue remodeling (matrix metalloproteinases 3/9/10, urokinase receptor), endothelial activation (E-selectin), T-cell activation (IL2RA), neutrophil activation (myeloperoxidase), lipid metabolism (FABP4), and growth factors (FGF21, transforming growth factor-α). Total numbers of dysregulated proteins were smaller in pediatric AD (n = 22) than in adult AD (n = 61). Clinical severity scores were positively correlated with receptors for interleukins 33 and 36 and inversely correlated with some Th1 markers (interferon gamma, CXCL11).
Different baseline expression levels in healthy pediatric vs adult samples.
Within months of pediatric AD onset, systemic immune activation is present, with Th2/Th17 skewing but otherwise different proteomic patterns from adult AD. Future correlation of proteomic patterns with disease course, comorbidity development, and drug response may yield predictive biomarkers.
尽管越来越多的证据表明,患有长期特应性皮炎(AD)的成年人存在系统性炎症,但对于近期发病的早期儿科 AD 患者的系统性炎症知之甚少。
分析早期儿科 AD 的血液炎症蛋白。
我们使用高通量蛋白质组学(邻近延伸分析),比较了 30 名年龄在 5 岁以下(发病后 6 个月内)、中重度 AD 儿童与年龄匹配的儿科对照个体和 AD 成人患者的血液中 257 种炎症和心血管风险蛋白。
在儿科 AD 患者的血液中,辅助性 T 细胞(Th)2 型(CCL13、CCL22)和 Th17 型(肽酶抑制剂 3/Elafin)标志物增加,同时伴有组织重塑标志物(基质金属蛋白酶 3/9/10、尿激酶受体)、内皮细胞激活标志物(E-选择素)、T 细胞激活标志物(IL2RA)、中性粒细胞激活标志物(髓过氧化物酶)、脂质代谢标志物(FABP4)和生长因子标志物(FGF21、转化生长因子-α)。儿科 AD(n=22)患者失调蛋白总数少于成人 AD(n=61)患者。临床严重程度评分与白细胞介素 33 和 36 的受体呈正相关,与某些 Th1 标志物(干扰素γ、CXCL11)呈负相关。
健康儿科与成人样本的基线表达水平不同。
在儿科 AD 发病后数月内,存在全身免疫激活,表现为 Th2/Th17 偏向,但与成人 AD 的蛋白质组学模式不同。未来对蛋白质组学模式与疾病进程、合并症发展和药物反应的相关性研究可能会产生预测生物标志物。