Impact of filaggrin mutations on Raman spectra and biophysical properties of the stratum corneum in mild to moderate atopic dermatitis
Impact of filaggrin mutations on Raman spectra and biophysical properties of the stratum corneum in mild to moderate atopic dermatitis
复制标题
DOI：
10.1111/j.1468-3083.2011.04198.x
复制
发表时间：
2012-08-01
影响因子：
9.2
通讯作者：
Tschachler, E.
中科院分区：
文献类型：
--
作者：
Mlitz, V.;Latreille, J.;Tschachler, E.
背景 特应性皮炎 (AD) 与聚丝蛋白 (FLG) 基因的无效突变有关。目的 评估 FLG 无效突变对健康个体和 AD 患者的生物物理特性和角质层 (SC) 分子组成的影响。方法 对总共 196 名法国成年人（其中 97 名有轻度至中度 AD 病史）进行了三种主要欧洲 FLG 突变的基因分型。使用拉曼光谱测定 SC 中天然保湿因子 (NMF) 的成分、脂质和水含量。此外，还测量了 SC 的经表皮失水量、电容和 pH 值。结果 AD 患者角质层总 NMF、水、鸟氨酸和尿刊酸 (UCA) 浓度显着低于健康对照。在 4% 的对照者和 10% 的 AD 患者中检测到 FLG 无效突变。 FLG 突变与 AD 患者 SC 乳酸水平升高、大多数其他 NMF 成分浓度降低以及疾病严重程度升高相关。在没有FLG突变的AD患者中，NMF成分的含量随着疾病严重程度的增加而减少。 SC 中同时存在低浓度的组氨酸、丙氨酸以及甘氨酸或吡咯烷酮 5-羧酸 (PCA) 与 FLG 突变相关，特异性为 92%。结论 我们的研究结果表明，轻度 AD 中 FLG 突变的发生率较低，并支持丝聚蛋白在确定 SC 理化参数中的重要作用。 SC 中几种聚丝蛋白分解产物的联合测量可能有助于特异性预测 FLG 突变的存在。
Background Atopic dermatitis (AD) is associated with null mutations in the filaggrin (FLG) gene. Objective To assess the impact of FLG null mutations on biophysical properties and the molecular composition of the stratum corneum (SC) in healthy individuals and AD patients. Methods A total of 196 French adults, including 97 with a history of mild to moderate AD, were genotyped for the three major European FLG mutations. Components of the natural moisturizing factor (NMF), lipids and water content in the SC were determined using Raman spectroscopy. In addition, trans-epidermal water loss, capacitance and pH of the SC were measured. Results Stratum corneum concentrations of total NMF, water, ornithine and urocanic acid (UCA) were significantly lower in AD patients than in healthy controls. Null mutations of FLG were detected in 4% of controls and 10% of AD patients. FLG mutations were associated with increased SC levels of lactate, reduced concentrations of most other NMF components and higher disease severity in AD patients. In AD patients without FLG mutations, the content of NMF constituents decreased with increasing disease severity. The concomittant presence of low concentrations of histidine, alanine and either glycine or pyrrolidone-5-carboxylic acid (PCA) in the SC was associated with FLG mutations with 92% specificity. Conclusions Our findings suggest a low prevalence of FLG mutations in mild AD and support an important role for filaggrin in determining the physicochemical parameters of the SC. The combined measurement of several filaggrin breakdown products in the SC may be useful to specifically predict the presence of FLG mutations.