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.
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.
Ortiz-Urda
Susana
S
Department of Dermatology, University of Vienna, Vienna, Austria. sortiz@cmgm.stanford.edu
Elbe-Bürger
Adelheid
A
Smolle
Josef
J
Marquart
Yvonne
Y
Chudnovsky
Yakov
Y
Ridky
Todd W
TW
Bernstein
Pamela
P
Wolff
Klaus
K
Rappersberger
Klemens
K
D000287:Administration, Topical; D000818:Animals; D001323:Autoantibodies / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D015820:Cadherins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D002241:Carbohydrates / Q000276:immunology; D002478:Cells, Cultured; D051183:Desmoglein 1; D004195:Disease Models, Animal; D006031:Glycosylation; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009924:Organ Culture Techniques; D010392:Pemphigus / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D011485:Protein Binding / Q000276:immunology; D014183:Transplantation, Heterologous; D014909:Wheat Germ Agglutinins / Q000008:administration & dosage / Q000494:pharmacology*
D001323:Autoantibodies; D001324:Autoantigens; D015820:Cadherins; D002241:Carbohydrates; D051183:Desmoglein 1; D007106:Immune Sera; D007166:Immunosuppressive Agents; D014909:Wheat Germ Agglutinins