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The Journal of Immunology, 2003, 171: 6244-6250.
Copyright © 2003 by The American Association of Immunologists

The Plant Lectin Wheat Germ Agglutinin Inhibits the Binding of Pemphigus Foliaceus Autoantibodies to Desmoglein 1 in a Majority of Patients and Prevents Pathomechanisms of Pemphigus Foliaceus In Vitro and In Vivo

Susana Ortiz-Urda1,*,{ddagger}, Adelheid Elbe-Bürger{dagger}, Josef Smolle§, Yvonne Marquart*, Yakov Chudnovsky{ddagger}, Todd W. Ridky{ddagger}, Pamela Bernstein{ddagger}, Klaus Wolff* and Klemens Rappersberger*

Divisions of * General Dermatology and {dagger} Immunodermatology, Department of Dermatology, University of Vienna, Vienna, Austria; {ddagger} Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305; § Division of Analytic Morphologic Dermatology, Department of Dermatology, University of Graz, Graz, Austria; and Department of Dermatology, Hospital Rudolfstiftung, Vienna, Austria

Pemphigus foliaceus (PF) is a life-threatening autoimmune blistering skin disease caused by pathogenic IgG autoantibodies against desmoglein 1 (dg1), a desmosomal cadherin-type adhesion glycoprotein. Using lectins and glycosidases, we have shown that dg1 displays an N-glycosylation pattern of the complex triantennary type. We have found that lectins and glycosidases interfere with N-bound sugar residues on the amino-terminal ectodomain of dg1 and completely abolish, in vitro, the antigenicity of dg1 in most of the patients’ sera. Moreover, in an ex vivo model using punch biopsies from normal human skin, we demonstrate that preincubation of the epidermis in wheat germ agglutinin (WGA) prevents PF autoantibody binding, acantholysis, and subcorneal blistering. In addition, we show that topical treatment with WGA inhibits PF autoantibody binding to keratinocytes in both newborn BALB/c mice and in organotypic human epidermis grafted onto the back of SCID mice. The epidermis of these pretreated animals displays a regular morphology, whereas control animals develop the immunopathologic phenotype of PF. These findings suggest that WGA may interfere with autoantibody binding to dg1, preventing experimental PF without affecting the adhesive function of dg1. Our observations may provide a new approach to the therapy of PF.




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R. Uematsu, J.-i. Furukawa, H. Nakagawa, Y. Shinohara, K. Deguchi, K. Monde, and S.-I. Nishimura
High Throughput Quantitative Glycomics and Glycoform-focused Proteomics of Murine Dermis and Epidermis
Mol. Cell. Proteomics, December 1, 2005; 4(12): 1977 - 1989.
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