Autoimmunity to keratinocyte acetylcholine receptors in pemphigus

Pemphigus autoimmunity is not limited to antidesmoglein antibodies. Nondesm oglein antibodies induce pemphigus-like lesions in neonatal mice. Acantholy tic activity of pemphigus IgG harbors pharmacologic effects on keratinocyte shape and adhesion. Acantholytic antireceptor autoantibodies target: (1) a novel human alpha9 acetytcholine receptor regulating keratinocyte adhesion , and (2) pemphaxin, a novel keratinocyte annexin-like molecule binding ace tylcholine. A 'multiple-hit' hypothesis reconciles recent findings of anti- acetylcholine-receptor autoimmunity in pemphigus and the fact that pemphigu s patients also develop autoantibodies to adhesion molecules. The antiacant holytic activity of cholinergic agonists suggests a novel avenue for the de velopment of a nonhormonal treatment of pemphigus. Copyright (C) 2000 S. Ka rger AG, Basel.