Pohla-Gubo G, Lazarova Z, Giudice G J, Liebert M, Grassegger A, Hintner H, Yancey K B
Department of Dermatology, Salzburg, Austria.
Exp Dermatol. 1995 Aug;4(4 Pt 1):199-206. doi: 10.1111/j.1600-0625.1995.tb00245.x.
Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal form of junctional epidermolysis bullosa characterized by generalized skin and mucosal blisters that heal with atrophy; other features include alopecia, nail dystrophy, large melanocytic nevi, and autosomal recessive inheritance. The specific aim of this study was to identify an abnormality in epidermal basement membrane adhesion molecules in well characterized GABEB patients that would explain why these subjects' epidermis separates from their epidermal basement membrane. Cryostat sections of nonlesional skin from 8 GABEB patients in 5 different families as well as skin from normal volunteers (controls) were studied by indirect immunofluorescence microscopy using rabbit antiserum directed against a BPAG1 fusion protein or monoclonal antibodies directed against the extracellular domain of BPAG2 (HD18 and 233), epiligrin (P1E1), laminin 5 (GB3), types IV and VII collagen, or integrin subunits alpha 2, alpha 3, beta 1, alpha 6, or beta 4. In these studies, monoclonal antibodies HD18 and 233 showed no reactivity and diminished reactivity, respectively, to the epidermal BM of all GABEB patients. Interestingly, in one patient, the absent or diminished reactivities of monoclonal anti-BPAG2 antibodies were limited to well demarcated portions of an otherwise intact epidermal basement membrane. Moreover, BPAG1, epiligrin, laminin 5, types IV and VII collagen, and all integrin subunits under study were expressed in the same manner in both GABEB and normal human skin. These findings identify an abnormality in the extracellular domain of BPAG2 in the skin of GABEB patients. BPAG2 (type XVII collagen) is a transmembrane, hemidesmosome-associated molecule whose extracellular domain resides at the exact level where blisters develop in the skin of patients with GABEB.(ABSTRACT TRUNCATED AT 250 WORDS)
泛发性萎缩性良性大疱性表皮松解症（GABEB）是交界性大疱性表皮松解症的一种非致死形式，其特征为全身性皮肤和黏膜水疱，愈合后出现萎缩；其他特征包括脱发、甲营养不良、巨大黑素细胞痣以及常染色体隐性遗传。本研究的具体目的是在特征明确的GABEB患者中鉴定表皮基底膜黏附分子的异常情况，以解释为何这些患者的表皮会与其表皮基底膜分离。采用间接免疫荧光显微镜技术，使用针对BPAG1融合蛋白的兔抗血清或针对BPAG2细胞外结构域（HD18和233）、表皮整联配体蛋白（P1E1）、层粘连蛋白5（GB3）、IV型和VII型胶原或整合素亚基α2、α3、β1、α6或β4的单克隆抗体，对来自5个不同家族的8例GABEB患者的非皮损皮肤冷冻切片以及正常志愿者（对照）的皮肤进行研究。在这些研究中，单克隆抗体HD18和233分别对所有GABEB患者的表皮基底膜无反应性和反应性减弱。有趣的是，在1例患者中，单克隆抗BPAG2抗体反应缺失或减弱仅限于原本完整的表皮基底膜的界限分明的部分。此外，BPAG1、表皮整联配体蛋白、层粘连蛋白5、IV型和VII型胶原以及所有研究的整合素亚基在GABEB患者和正常人皮肤中的表达方式相同。这些发现确定了GABEB患者皮肤中BPAG2细胞外结构域的异常。BPAG2（XVII型胶原）是一种跨膜的、与半桥粒相关的分子，其细胞外结构域恰位于GABEB患者皮肤水疱形成的水平。（摘要截取自250词）
