Autoimmunity against desmosomal cadherins in pemphigus
Autoimmunity against desmosomal cadherins in pemphigus
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DOI：
10.1016/s0923-1811(99)00016-x
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发表时间：
1999-06-01
影响因子：
4.6
通讯作者：
Amagai, M
中科院分区：
文献类型：
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作者：
Amagai, M
天疱疮是一种独特而有趣的自身免疫性疾病，其中自身抗体起主要致病作用并导致水疱形成。近年来天疱疮的研究取得了显著进展，从分子水平上对天疱疮临床观察中提出的几个问题进行了逻辑回答。经典型天疱疮，寻常型天疱疮（PV）和落叶型天疱疮（PF）的临床表型由抗桥粒芯糖蛋白自身抗体谱定义。单独含有抗Dsg 3 IgG的血清会导致粘膜为主的PV，但皮肤受累有限。同时含有抗Dsg 3和抗Dsg 1的血清可引起粘膜皮肤PV，其影响皮肤和粘膜。仅含有抗Dsg 1的血清引起PF，其显示皮肤但不涉及粘膜。在疱疹样天疱疮（HP）中，大多数血清识别Dsg 1，其余的识别Dsg 3，表明HP是PF或PV的临床变异体。副肿瘤性天疱疮（PNP）患者具有针对多种分子的自身抗体。现在我们知道他们有针对斑蛋白家族所有成员的自身抗体，斑蛋白家族是细胞质蛋白，包括桥粒斑蛋白、BPAG 1、包斑蛋白、周斑蛋白和网斑蛋白。最终发现了引起水泡的致病性自身抗体攻击的PNP的细胞表面靶抗原是Dsg 3和Dsg 1。因此，PNP被表征为针对斑蛋白分子和桥粒芯糖蛋白的自身免疫性疾病。伊加天疱疮的自身免疫靶点可能比最初认为的更异质。目前已知桥粒胶蛋白1、Dsg 3和Dsg 1是它们的靶抗原。因此，天疱疮已成为一种组织特异性自身免疫性疾病。天疱疮将是下一个世纪解决自身免疫性疾病和基础免疫学的中心问题的一个很好的模型疾病;为什么以及如何患有自身免疫性疾病的患者开始将自我识别为非自我！(C)1999爱思唯尔科学爱尔兰有限公司保留所有权利。
Pemphigus is a unique and interesting autoimmune disease, in which autoantibodies play a major pathogenic role and cause blister formation. Several questions raised from clinical observation in pemphigus have been answered with logic at the molecular level owing to recent remarkable progress in research in the field of pemphigus. The clinical phenotype of classic pemphigus, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), is defined by anti-desmoglein autoantibody profile. Sera containing anti-Dsg3 IgG alone cause mucosal dominant PV with limited skin involvement. Sera containing both anti-Dsg3 and anti-Dsg1 cause mucocutaneous PV, which affects both the skin and mucous membrane. Sera containing only anti-Dsg1 cause PF, which shows cutaneous but no mucosal involvement. In herpetiform pemphigus (HP) most sera recognize Dsg1 and the rest of them recognize Dsg3, indicating that HP is a clinical variant of PF or PV. Patients with paraneoplastic pemphigus (PNP) have autoantibodies against multiple molecules. Now we know that they have autoantibodies against all members of the plakin family, which are cytoplasmic proteins and include desmoplakin, BPAG1, envoplakin, periplakin and plectin. Cell surface target antigens of PNP, which blister-inducing pathogenic autoantibodies attack, were finally discovered to be Dsg3 and Dsg1. Therefore, PNP is characterized as an autoimmune disease against plakin molecules and desmogleins. Autoimmune targets of IgA pemphigus are likely more heterogeneous than originally thought. So far, desmocollin 1, Dsg3, and Dsg1 are known as their target antigens. Thus, pemphigus has become one of well-characterized tissue-specific autoimmune diseases. Pemphigus will be a good model disease in the next century to address the central issue of autoimmune disease and basic immunology; why and how do patients with autoimmune diseases start to recognize self as non-self! (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.