Autoimmunity to Keratinocyte Acetylcholine Receptors in Pemphigus

Pemphigus autoimmunity is not limited to antides- moglein antibodies. Nondesmoglein antibodies induce pemphigus-like lesions in neonatal mice. Acantholytic activity of pemphigus IgG harbors pharmacologic effects on keratinocyte shape and adhesion. Acantholytic antireceptor autoantibodies target: (1) a novel human alpha9 acetylcholine receptor regulating keratinocyte adhesion, and (2) pemphaxin, a novel keratinocyte annexin-like molecule binding acetylcholine. A 'multiple-hit' hypothesis reconciles recent findings of anti-acetylcholine-receptor autoimmunity in pemphigus and the fact that pemphigus patients also develop autoantibodies to adhesion molecules. The antiacantholytic activity of cholinergic agonists suggests a novel avenue for the development of a nonhormonal treatment of pemphigus.