Rubenstein David S, Diaz Luis A
Department of Dermatology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599-7287, USA.
Autoimmunity. 2006 Nov;39(7):577-86. doi: 10.1080/08916930600971885.
The pemphigus family of autoimmune blistering diseases is characterized by an autoantibody response to desmosomal cadherins in epithelia. Autoantibodies against desmogleins, desmosome cell adhesion molecules, induce loss of cell-cell adhesion that is characterized clinically by blister formation. The mechanism by which these autoantibodies induce loss of cell-cell adhesion is under active investigation, but appears to involve a coordinated intracellular response including activation of intracellular signaling and phosphorylation of a number of proteins in the target keratinocyte. Activation of p38 mitogen activated protein kinase may have a critical role in the acantholytic mechanism as inhibitors of p38MAPK block the ability of pemphigus IgG to induce blistering in pemphigus animal models.
自身免疫性水疱病天疱疮家族的特征是上皮细胞中针对桥粒钙黏蛋白产生自身抗体反应。针对桥粒芯糖蛋白(一种桥粒细胞黏附分子)的自身抗体可导致细胞间黏附丧失,临床上表现为水疱形成。这些自身抗体诱导细胞间黏附丧失的机制正在积极研究中,但似乎涉及细胞内的协同反应,包括细胞内信号传导的激活以及靶角质形成细胞中多种蛋白质的磷酸化。p38丝裂原活化蛋白激酶的激活在棘层松解机制中可能起关键作用,因为p38丝裂原活化蛋白激酶抑制剂可阻断天疱疮IgG在天疱疮动物模型中诱导水疱形成的能力。