Autoantibody Signaling in Pemphigus Vulgaris: Development of an Integrated Model.
Autoantibody Signaling in Pemphigus Vulgaris: Development of an Integrated Model.
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DOI：
10.3389/fimmu.2018.00692
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发表时间：
2018
影响因子：
7.3
通讯作者：
Sinha AA
中科院分区：
文献类型：
--
作者：
Sajda T;Sinha AA
寻常型天疱疮是一种影响皮肤和粘膜上皮的自身免疫性皮肤水疱性疾病。已知PV中的水疱形成是由自身抗体（autoAb）与角质形成细胞抗原结合引起的。已知致病性自身抗体的主要抗原靶标是桥粒芯糖蛋白3，并且在较小程度上是桥粒芯糖蛋白1，部分包含桥粒的钙粘蛋白家族蛋白，桥粒是负责维持细胞粘附的蛋白质结构，尽管还已知PV患者中存在其他自身抗体，其在水疱形成中的作用尚不清楚。然而，关于自身抗体结合诱导水疱形成的精确机制的知识仍存在很大差距。因此，PV的主要治疗干预措施集中在全身免疫抑制，其副作用对患者构成重大健康风险。为了鉴定新的疾病特异性治疗靶点，大量研究试图阐明autoAb结合下游的致病机制，导致了对autoAb介导的水疱形成的理解的显著进步。尽管这种增强的表征疾病的过程中，一个令人满意的解释autoAb诱导的棘层松解仍然不存在。在这里，我们仔细回顾了文献调查的致病性疾病的机制，在PV，并考虑到从这些研究的结果的全部范围，提供了一个新的，全面的理论，在PV水疱形成。
Pemphigus vulgaris (PV) is an autoimmune skin blistering disease effecting both cutaneous and mucosal epithelia. Blister formation in PV is known to result from the binding of autoantibodies (autoAbs) to keratinocyte antigens. The primary antigenic targets of pathogenic autoAbs are known to be desmoglein 3, and to a lesser extent, desmoglein 1, cadherin family proteins that partially comprise the desmosome, a protein structure responsible for maintaining cell adhesion, although additional autoAbs, whose role in blister formation is still unclear, are also known to be present in PV patients. Nevertheless, there remain large gaps in knowledge concerning the precise mechanisms through which autoAb binding induces blister formation. Consequently, the primary therapeutic interventions for PV focus on systemic immunosuppression, whose side effects represent a significant health risk to patients. In an effort to identify novel, disease-specific therapeutic targets, a multitude of studies attempting to elucidate the pathogenic mechanisms downstream of autoAb binding, have led to significant advancements in the understanding of autoAb-mediated blister formation. Despite this enhanced characterization of disease processes, a satisfactory explanation of autoAb-induced acantholysis still does not exist. Here, we carefully review the literature investigating the pathogenic disease mechanisms in PV and, taking into account the full scope of results from these studies, provide a novel, comprehensive theory of blister formation in PV.
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影响因子：
3.3
作者：
Braga, VMM;Betson, M;Lamarche-Vane, N
通讯作者：
Lamarche-Vane, N
影响因子：
10.3
作者：
Baroni, A;Buommino, E;Ruocco, V
通讯作者：
Ruocco, V
影响因子：
4.8
作者：
Berkowitz, P;Hu, PQ;Rubenstein, DS
通讯作者：
Rubenstein, DS
影响因子：
64.5
作者：
AMAGAI, M;KLAUSKOVTUN, V;STANLEY, JR
通讯作者：
STANLEY, JR
影响因子：
3.6
作者：
Ahmed, A. Razzaque;Carrozzo, Marco;Grando, Sergei A.
通讯作者：
Grando, Sergei A.