Antibodies against the adhesion molecule desmoglein 3 (Dsg 3) are sufficient to induce the characteristic lesions of pemphigus vulgaris (PV), a severe autoimmune disease that causes skin and mucous membrane blistering. Caldelari et al. (page 823) have now developed an in vitro system to study PV, and have found that plakoglobin is required to mediate the keratin retraction and loss of cellular adhesion caused by anti–Dsg 3 (PV IgG) antibodies. The findings contradict one of the two major models of PV pathogenesis, and also indicate that plakoglobin is required for maintaining normal tissue architecture.
The simplest explanation for the action of PV IgG is that antibody binding sterically hinders Dsg 3–mediated cell adhesion, leading to the formation of blisters. But the antibodies also interfere with intracellular events, so it remained unclear whether PV blister formation was caused solely by...
