ICHTHYOSIS VULGARIS - IDENTIFICATION OF A DEFECT IN SYNTHESIS OF FILAGGRIN CORRELATED WITH AN ABSENCE OF KERATOHYALINE GRANULES
ICHTHYOSIS VULGARIS - IDENTIFICATION OF A DEFECT IN SYNTHESIS OF FILAGGRIN CORRELATED WITH AN ABSENCE OF KERATOHYALINE GRANULES
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DOI：
10.1111/1523-1747.ep12264813
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发表时间：
1985-01-01
影响因子：
6.5
通讯作者：
HOLBROOK, KA
中科院分区：
文献类型：
--
作者：
SYBERT, VP;DALE, BA;HOLBROOK, KA
寻常型鱼鳞病是一种常染色体显性的角化疾病，其组织学特征是表皮角化蛋白颗粒缺失或减少和轻度角化过度。寻常型鱼鳞病的基本缺陷尚不清楚。对2个寻常型鱼鳞病家族患者表皮中聚丝蛋白及其前体聚丝蛋白（profilaggrin）的含量进行了检测，发现聚丝蛋白及其前体聚丝蛋白（profilaggrin）的含量及其相对数量与同一个体的超微结构结果相关。聚丝蛋白存在于染色的十二烷基硫酸钠凝胶和来自对照和未受影响的家庭成员表皮蛋白的免疫印迹上。在每个家庭中，受影响较严重的个体没有这种症状，而在受影响较轻的家庭成员中，这种症状的强度有所降低。对照组的免疫组织学显示，聚丝蛋白相关蛋白定位于角质层和颗粒层内。相比之下，受影响个体的组织几乎没有反应。EM研究显示，3例重度患者没有角膜透明素颗粒，其余患者角膜透明素颗粒数量减少。电镜下角膜透明素的相对量与免疫印迹检测到的聚丝蛋白的量相关。角质层比正常人厚，但显示出典型的角蛋白模式染色，这表明聚丝蛋白不是角蛋白丝聚集所必需的，可能在体内有其他功能。寻常型鱼鳞病2个家系的5例患者结构蛋白，侧聚蛋白和聚丝蛋白均减少或缺失。这种生化异常与角膜透明素量的形态学减少和疾病的临床严重程度有关。
Ichthyosis vulgaris is an autosomal dominant disorder of keratinization characterized histologically by absent or reduced keratohyaline granules in the epidermis and mild hyperkeratosis. The basic defect in ichthyosis vulgaris is unknown. The presence of filaggrin and its precursor, profilaggrin was tested for in the epidermis of affected and unaffected individuals from 2 families with ichthyosis vulgaris and its presence and relative quantity was correlated with ultrastructure findings in the same individuals. Filaggrin was present on stained sodium dodecyl sulfate gels and immunoblots of epidermal proteins from controls and unaffected family members. It was absent from the more severely affected individuals in each family and reduced in intensity in the less severely affected family members. Immunohistology in controls showed localization of filaggrin-related protein in the stratum corneum and within the granular layer. In contrast, tissue from affected individuals showed little or no reaction. EM studies showed that keratohyaline granules were absent in 3 severely affected individuals, and reduced in number in the others. The relative amount of keratohyalin by electron microscopy correlated with the amount of filaggrin detectable on immunoblots. The stratum corneum was thicker than in normals but showed the typical keratin pattern staining suggesting that filaggrin is not essential for keratin filament aggregation and may have another function in vivo. The structural proteins, profilaggin and filaggrin, are reduced or absent in 5 patients from 2 pedigrees with ichthyosis vulgaris. This biochemical abnormality correlates with the morphologic reduction in the amount of keratohyalin and with the clinical severity of the disorder.