Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology
Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology
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DOI：
10.1111/exd.13106
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发表时间：
2016-11-01
影响因子：
3.6
通讯作者：
Grando, Sergei A.
中科院分区：
文献类型：
--
作者：
Ahmed, A. Razzaque;Carrozzo, Marco;Grando, Sergei A.
这种观点强调了关于天疱疮发病机制的主要的、部分有争议的概念。单病原理论通过桥粒芯糖蛋白（Dsg）补偿假说解释了表皮内起泡，根据该假说，Dsg 1和/或Dsg 3介导的角质形成细胞（KC）的细胞-细胞附着的抗体依赖性失能足以破坏表皮完整性并引起起泡。多病原体理论通过多击假说解释了表皮内水疱，该假说指出调节和/或介导KC细胞间粘附的生理机制的同时和同步失活对于破坏表皮完整性是必要的。多病原体理论的主要前提是，单一类型的自身抗体只诱导可逆的变化，因此受影响的KC可以通过自我修复恢复。然而，当补救途径和/或其他细胞功能被伙伴自身抗体和/或其他致病因子改变时，损伤变得不可逆。未来的研究需要（i）证实这些发现，（ii）详细描述非Dsg特异性自身抗体的患者人群，（iii）确定非Dsg抗体在疾病病理生理学中的贡献程度。
This viewpoint highlights major, partly controversial concepts about the pathogenesis of pemphigus. The monopathogenic theory explains intra-epidermal blistering through the desmoglein (Dsg) compensation hypothesis, according to which an antibody-dependent disabling of Dsg 1- and/or Dsg 3-mediated cell-cell attachments of keratinocytes (KCs) is sufficient to disrupt epidermal integrity and cause blistering. The multipathogenic theory explains intra-epidermal blistering through the multiple hit hypothesis stating that a simultaneous and synchronized inactivation of the physiological mechanisms regulating and/or mediating intercellular adhesion of KCs is necessary to disrupt epidermal integrity. The major premise for a multipathogenic theory is that a single type of autoantibody induces only reversible changes, so that affected KCs can recover due to a self-repair. The damage, however, becomes irreversible when the salvage pathway and/or other cell functions are altered by a partnering autoantibody and/or other pathogenic factors. Future studies are needed to (i) corroborate these findings, (ii) characterize in detail patient populations with non-Dsg-specific autoantibodies, and (iii) determine the extent of the contribution of non-Dsg antibodies in disease pathophysiology.