Pathogenicity and epitope characteristics of anti-desmoglein-1 from pemphigus foliaceus patients expressing only IgG1 autoantibodies
Pathogenicity and epitope characteristics of anti-desmoglein-1 from pemphigus foliaceus patients expressing only IgG1 autoantibodies
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DOI：
10.1111/j.1523-1747.2003.12608.x
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发表时间：
2003-12-01
影响因子：
6.5
通讯作者：
Lin, MS
中科院分区：
文献类型：
--
作者：
Hacker-Foegen, MK;Janson, M;Lin, MS
叶型天疱疮是一种抗体介导的自身免疫性疾病，抗桥粒糖蛋白桥粒蛋白-1(DSG1)的自身抗体以IgG1和IgG4为主。以前，我们发现，在被动转移动物模型中，抗DSG1的IgG4型自身抗体只识别构象表位(S)，而IgG1型自身抗体既识别构象表位又识别线性表位，但不显示致病性。本研究的目的是分析在整个病程中只表达IgG1同型抗DSG1的PF患者的自身抗体识别的表位，并进一步表征他们的IgG1抗DSG1的致病性。我们发现，这一亚群PF患者中的IgG1自身抗体，与其他PF患者的IgG4自身抗体相似，能够与人和小鼠的皮肤结合，并在小鼠体内诱导实验性PF。此外，详细的表位图显示，这些PF患者的IgG1自身抗体识别的构象表位仅限于DSG1的前161个氨基酸，而线性表位分布在整个胞外区域。综上所述，我们的研究表明，免疫球蛋白同种类型并不一定决定天疱疮自身抗体的表位和致病性。
Pemphigus foliaceus (PF) is an antibody-mediated autoimmune disorder with IgG1 and IgG4 as the predominant subclasses of autoantibodies against a desmosomal glycoprotein, desmoglein-1 (Dsg1). Previously, we found that the IgG4 anti-Dsg1 autoantibodies only recognize a conformational epitope(s), whereas the IgG1 autoantibodies recognize both conformational and linear epitopes but do not display pathogenicity in the passive transfer animal model. The purpose of this study was to analyze the epitopes recognized by autoanti-bodies from a subset of PF patients who only express anti-Dsg1 of the IgG1 isotype throughout the course of their diseases and to further characterize the pathogenicity of their IgG1 anti-Dsg1. We found that IgG1 auto-antibodies in this subset of PF patients, similar to IgG4 autoantibodies from other PF patients, are able to bind both human and mouse skin and induce the experimental PF in mice. Moreover, a detailed epitope mapping reveals that the conformational epitopes recognized by IgG1 autoantibodies from these PF patients are restricted to the first 161 amino acids of Dsg1, whereas the linear epitopes are spread throughout the entire ectodomain. In conclusion, our study reveals that the isotype of IgG does not necessarily determine the epitopes and pathogenicity of pemphigus autoantibodies.