title: The anti-desmoglein 1 autoantibodies in pemphigus vulgaris sera are pathogenic.
abstract: Pemphigus vulgaris and pemphigus foliaceus are two closely related, but clinically and histologically distinct, autoimmune skin diseases. The autoantigens for pemphigus vulgaris and pemphigus foliaceus are desmoglein 3 and desmoglein 1, respectively. The anti-desmoglein 1 antibodies in pemphigus foliaceus and anti-desmoglein 3 antibodies in pemphigus vulgaris are pathogenic as determined by immunoglobulin G passive transfer animal models. More than 50% of pemphigus vulgaris sera also contain anti-desmoglein 1 autoantibodies; however, the pathogenicity of the anti-desmoglein 1 autoantibodies in pemphigus vulgaris remains unknown. In this study, we used soluble recombinant extracellular domains of desmoglein 1 and desmoglein 3 to obtain affinity-purified anti-desmoglein 1 and anti-desmoglein 3 autoantibodies from pemphigus vulgaris sera and examined the pathogenicity of each fraction separately using the passive transfer mouse model. By immunoprecipitation, the purified anti-desmoglein 1 and anti-desmoglein 3 showed no cross-reactivity. The anti-desmoglein 1 autoantibodies in pemphigus vulgaris induced typical pemphigus foliaceus lesions in neonatal mice, whereas the anti-desmoglein 3 fraction induced pemphigus vulgaris-like lesions. In addition, the pathogenic anti-desmoglein 1 and anti-desmoglein 3 autoantibodies in pemphigus vulgaris had predominant IgG4 subclass specificity. These findings suggest that the anti-desmoglein 1 antibodies in pemphigus vulgaris are pathogenic.
authors.affiliation: Department of Dermatology, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: X
authors.initials: X
authors.lastname: Ding
authors.forename: L A
authors.initials: LA
authors.lastname: Diaz
authors.forename: J A
authors.initials: JA
authors.lastname: Fairley
authors.forename: G J
authors.initials: GJ
authors.lastname: Giudice
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000051:Acantholysis / Q000276:immunology / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D015820:Cadherins / Q000096:biosynthesis / Q000276:immunology*; D051183:Desmoglein 1; D051184:Desmoglein 3; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010392:Pemphigus / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000302:isolation & purification
chemical_list: D001323:Autoantibodies; D015820:Cadherins; C071894:DSG3 protein, human; D051183:Desmoglein 1; D051184:Desmoglein 3; D007074:Immunoglobulin G; D011994:Recombinant Proteins