McGrath J A, Ishida-Yamamoto A, O'Grady A, Leigh I M, Eady R A
Department of Cell Pathology, United Medical School, St. Thomas's Hospital, London, U.K.
J Invest Dermatol. 1993 Apr;100(4):366-72. doi: 10.1111/1523-1747.ep12471830.
Dystrophic epidermolysis bullosa is characterized by various abnormalities of anchoring fibrils, which are mainly composed of type VII collagen, at the dermal-epidermal junction. To define these changes more clearly, we examined skin samples from 22 patients with different forms of dystrophic epidermolysis bullosa by pre-embedding immunoelectron microscopy using an antibody (LH 7:2) that binds to the NC-1 globular domain of type VII collagen, followed by 1 nm colloidal gold-labeled secondary antibodies and subsequent silver enhancement. In dominant dystrophic epidermolysis bullosa cases, there was only a slight but variable reduction in the immunolabeling density on anchoring fibrils and on the lamina densa, in parts similar to normal human skin. In localized recessive dystrophic epidermolysis bullosa skin, some fibrillar structures just below the lamina densa (and particularly subjacent to hemidesmosomes) had specific antibody labeling despite their lack of resemblance to definitive anchoring fibrils. Immunolabeling with LH 7:2 was also seen within basal keratinocyte endoplasmic reticulum and cytoplasmic vesicles in some dystrophic epidermolysis bullosa patients, usually with milder phenotypic features. Even in the most severe cases of generalized recessive dystrophic epidermolysis bullosa, occasional immunolabeling was found within the lamina densa and on scanty thin filamentous structures at sub-lamina densa sites usually occupied by anchoring fibrils. This study suggests that dystrophic epidermolysis bullosa patients express some type VII collagen NC-1 domain epitopes that may be variably reduced at the dermal-epidermal junction or retained within basal keratinocytes. The clinical heterogeneity in dystrophic epidermolysis bullosa is mirrored by a range of immunoelectron microscopy findings, indicating variability in completeness of anchoring fibril formation and a possible spectrum of underlying type VII collagen structural protein abnormalities.
营养不良性大疱性表皮松解症的特征是真皮 - 表皮交界处的锚定原纤维存在各种异常，锚定原纤维主要由VII型胶原蛋白组成。为了更清楚地定义这些变化，我们使用一种与VII型胶原蛋白的NC - 1球状结构域结合的抗体（LH 7:2），通过包埋前免疫电子显微镜检查了22例不同形式营养不良性大疱性表皮松解症患者的皮肤样本，随后用1nm胶体金标记的二抗进行处理并进行银增强。在显性营养不良性大疱性表皮松解症病例中，锚定原纤维和致密板上的免疫标记密度仅有轻微但可变的降低，部分区域与正常人类皮肤相似。在局限性隐性营养不良性大疱性表皮松解症皮肤中，致密板下方（特别是半桥粒下方）的一些纤维状结构尽管与确定的锚定原纤维不同，但有特异性抗体标记。在一些营养不良性大疱性表皮松解症患者的基底角质形成细胞内质网和细胞质小泡内也可见LH 7:2免疫标记，这些患者通常具有较轻的表型特征。即使在最严重的泛发性隐性营养不良性大疱性表皮松解症病例中，在致密板内以及通常由锚定原纤维占据的致密板下部位的少量细纤维状结构上也偶尔发现免疫标记。这项研究表明，营养不良性大疱性表皮松解症患者表达一些VII型胶原蛋白NC - 1结构域表位，这些表位在真皮 - 表皮交界处可能会有不同程度的减少，或者保留在基底角质形成细胞内。营养不良性大疱性表皮松解症的临床异质性反映在一系列免疫电子显微镜检查结果中，表明锚定原纤维形成的完整性存在差异以及潜在的VII型胶原蛋白结构蛋白异常可能存在一系列情况。
