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Giornale Italiano di Dermatologia e Venereologia 2007 August;142(4):345-52

Copyright © 2007 EDIZIONI MINERVA MEDICA

language: English

Cholinergic control of epidermal cell-cell adhesion in pemphigus

Kurzen H.

Department of Dermatology Venerology and Allergology Medical Faculty of Mannheim University of Heidelberg, Mannheim, Germany


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Pemphigus vulgaris (PV) is considered a scientifically highly attractive autoimmune disease based on the presence of pathogenetically relevant autoantibodies in the serum of patients that help to elucidate signaling events leading to clinically evident epidermal blister formation. There has been considerable debate on the mechanism of acantholysis starting with the classical view of desmogleins as main targets of PV autoimmunity, a view that is supported by the characterization of pathogenic antidesmoglein 3 antibodies from both patients and animal models. However, fundamental doubt has been raised towards this monopathogenic view, by several independent factors: 1) pemphigus lesions can be induced in Dsg3-knock-out mice; 2) pemphigus sera contain multiple autoantibodies against different adhesion molecules and also cholinergic receptors; 3) experimental inhibition of PV IgG induced acantholysis can be obtained by interference with different signaling cascades regulating both calcium homeostasis and apoptosis; 4) cholinergic agonists possess antiacantholytic activity both in vitro and in vivo. The field is open for controlled clinical trials and further basic research to unfold the true story of the pemphigus enigma and provide the basis for a better treatment of our pemphigus patients.

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