Pemphigus vulgaris antigen (Desmoglein 3) is localized in the lower epidermis, the site of blister formation in patients
Pemphigus vulgaris antigen (Desmoglein 3) is localized in the lower epidermis, the site of blister formation in patients
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DOI：
10.1111/1523-1747.ep12343081
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发表时间：
1996-02-01
影响因子：
6.5
通讯作者：
Stanley, JR
中科院分区：
文献类型：
--
作者：
Amagai, M;Koch, PJ;Stanley, JR
在寻常型天疱疮患者中，抗桥粒糖蛋白桥粒芯糖蛋白3（Dsg 3）的自身抗体由于较深表皮的基底层和紧邻基底上层中的角质形成细胞-细胞粘附的丧失而引起水疱，从而使浅表表皮保持完整。然而，来自这些患者的自身抗体通常与整个表皮的角质形成细胞的细胞表面结合，如通过间接免疫荧光所确定的。为了解释这一明显的矛盾，我们免疫吸附寻常天疱疮血清与重组杆状病毒感染的昆虫细胞产生的Dsg 3和桥粒芯糖蛋白1（Dsg 1）的胞外结构域。当与Dsg 3和Dsg 1的细胞外结构域吸附时，这些血清不再染色表皮，表明它们的细胞表面反应性的大部分（如果不是全部的话）可以归因于针对这些桥粒芯糖蛋白的细胞外结构域的抗体。仅用Dsg 1胞外结构域吸附留下的抗体仅染色表皮的基底层和直接基底上层，并且仅免疫沉淀Dsg 3，而不是Dsg 1，来自合成这些分子的培养细胞的提取物。相反，仅用Dsg 3胞外结构域吸附留下的抗体仅染色更浅表的表皮，并且仅免疫沉淀Dsg 1。这些数据将Dsg 3精确定位于寻常型天疱疮中发生水疱的表皮区域。
In patients with pemphigus vulgaris, autoantibodies against the desmosomal glycoprotein desmoglein 3 (Dsg3) cause blisters due to loss of keratinocyte cell-cell adhesion in the basal and immediate suprabasal layer of the deeper epidermis, leaving the superficial epidermis intact. Autoantibodies from these patients, however, usually bind to the cell surface of keratinocytes throughout the entire epidermis, as determined by indirect immunofluorescence. To explain this apparent paradox, we immunoadsorbed pemphigus vulgaris sera with the extracellular domains of Dsg3 and desmoglein 1 (Dsg1) produced by insect cells infected with recombinant baculovirus. When adsorbed with extracellular domains of both Dsg3 and Dsg1, these sera no longer stained epidermis, demonstrating that most, if not all, of their cell surface reactivity can be attributed to antibodies against the extracellular domains of these desmogleins. Adsorption with only the Dsg1 extracellular domain left antibodies that stained only the basal and immediate suprabasal layers of the epidermis and immunoprecipitated only Dsg3, not Dsg1, from extracts of cultured cells synthesizing these molecules, In contrast, adsorption with only the Dsg3 extracellular domain left antibodies that stained only the more superficial epidermis and immunoprecipitated only Dsg1. These data localize Dsg3 exactly Co the area in the epidermis where blisters occur in pemphigus vulgaris.