Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus
Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus
复制标题
DOI：
10.1111/1523-1747.ep12319025
复制
发表时间：
1997-08-01
影响因子：
6.5
通讯作者：
Nishikawa, T
中科院分区：
文献类型：
--
作者：
Hashimoto, T;Kiyokawa, C;Nishikawa, T
显示伊加抗角质形成细胞表面自身抗体的伊加天疱疮分为角膜下脓疱性皮肤病（SPD）和表皮内嗜中性伊加皮肤病（IEN）型。我们先前通过免疫印迹显示，来自一些伊加天疱疮患者的伊加与牛桥粒柯林斯（Dsc）反应，但不与人Dsc反应。为了确定伊加天疱疮的抗原，我们专注于Dsc的构象依赖性表位，因为经典天疱疮患者的血清识别桥粒芯糖蛋白的构象敏感性表位。我们构建了含有人Dsc 1、Dsc 2和Dsc 3的完整编码序列的哺乳动物表达载体，并通过脂质体转染将其瞬时转染入COS 7细胞。用单个人Dscs转染的COS7细胞的免疫荧光显示，所有6个SPD型伊加天疱疮病例的伊加抗体与表达Dsc1的细胞表面反应，但不与表达Dsc2或Dsc3的细胞反应。相比之下，七个IEN型伊加天疱疮病例中没有一个与用任何DSC转染的细胞反应。这些结果令人信服地表明，人Dsc 1是SPD型伊加天疱疮的自身抗原，这表明Dsc 1在这种疾病的发病机制中发挥重要作用的可能性。这项研究表明，Dsc可以成为人类皮肤病的自身免疫靶点。
IgA pemphigus showing IgA anti-keratinocyte cell surface autoantibodies is divided into subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic IgA dermatosis (IEN) types. We previously showed by immunoblotting that IgA from some IgA pemphigus patients reacted with bovine desmocollins (Dsc), but not human Dsc. To determine the antigen for IgA pemphigus, we focused on conformation-dependent epitopes of Dsc, because sera of patients with classical pemphigus recognize conformation-sensitive epitopes of desmogleins. We constructed mammalian expression vectors containing the entire coding sequences of human Dsc1, Dsc2, and Dsc3 and transiently transfected them into COS7 cells by lipofection. Immunofluorescence of COS7 cells transfected with single human Dscs showed that IgA antibodies of all six SPD-tppe IgA pemphigus cases reacted with the surface of cells expressing Dsc1, but not with cells expressing Dsc2 or Dsc3. In contrast, none of seven IEN-type IgA pemphigus cases reacted with cells transfected with any Dscs. These results convincingly indicate that human Dsc1 is an autoantigen for SPD-type IgA pemphigus, suggesting the possibility of an important role for Dsc1 in the pathogenesis of this disease. This study shows that a Dsc can be an autoimmune target in human skin disease.