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Vu Thuong Nguyen, PhD; Juan Arredondo, PhD; Alexander I. Chernyavsky, PhD; Mark R. Pittelkow, MD; Yasuo Kitajima, MD, PhD; Sergei A. Grando, MD, PhD, DSc

Arch Dermatol. 2004;140:327-334.

Background  Pemphigus vulgaris (PV) is an autoimmune, IgG autoantibody–mediated disease of skin and mucosa leading to progressive blistering and nonhealing erosions. Patients develop autoantibodies to adhesion molecules mediating intercellular adhesion and to keratinocyte cholinergic receptors regulating cell adhesion.

Observations  To determine whether a cholinergic agonist can abolish PV IgG–induced acantholysis, litter mates of neonatal athymic nude mice were injected with PV IgG together with carbachol (0.04 µg/g body weight). None of these mice developed skin lesions. Through in vitro experiments, we measured the expression of adhesion molecules in monolayers of normal human keratinocytes incubated overnight in the presence of 0.25mM carbachol using semiquantitative Western blot and immunofluorescence. Carbachol caused an elevation of the relative amount of E-cadherin in keratinocytes (P<.05) without changing that of plakoglobin (P>.05). The phosphorylation level of E-cadherin and plakoglobin was increased by PV IgG, whereas this effect of PV IgG was attenuated in the presence of 0.5mM carbachol. Pyridostigmine bromide, an acetylcholinesterase inhibitor, produced effects similar to those of carbachol, which helps explain its clinical efficacy in a patient with active PV that was resistant to treatment with systemic glucocorticosteroids. Treatment with pyridostigmine bromide (360 mg/d) in a patient with PV allowed to keep his disease under control at a lower dose of prednisone than that used before starting pyridostigmine bromide treatment.

Conclusion  Elucidation of the cholinergic control of keratinocyte adhesion merits further consideration because of a potential for the development of novel antiacantholytic therapies using cholinergic drugs.

From the Departments of Dermatology, University of California Davis, Sacramento (Drs Nguyen, Arredondo, Chernyavsky, and Grando), Mayo Clinic, Rochester, Minn (Dr Pittelkow), and Gifu University, Gifu City, Japan (Dr Kitajima). The authors have no relevant financial interest in this article.

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