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.
Grando
S A
SA
Department of Dermatology, University of California at Davis, Sacramento, CA 95817, USA. sagrando@ucdavis.edu
D000818:Animals; D015551:Autoimmunity; D002448:Cell Adhesion; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology*; D010392:Pemphigus / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*
D011950:Receptors, Cholinergic