title: Pathogenic human monoclonal antibody against desmoglein 3.
abstract: Pemphigus vulgaris (PV) is a potentially fatal autoimmune mucocutaneous disease associated with production of IgG autoantibodies to desmoglein 3 (Dsg3), a 130-kDa epidermal cadherin protein. The binding of pathogenic antibody to Dsg3 on epidermal keratinocytes leads to loss of intercellular adhesion and results in intraepithelial blister formation. Here, we describe a human monoclonal antibody, PVMAB786, a Dsg3-specific IgG4 antibody, from an untreated patient with active PV. The antibody reacts with a 130-kDa protein on keratinocyte cell surfaces and recombinant Dsg3 protein, but not desmoglein 1 protein. PVMAB786 induces acantholysis in normal human skin and mucous membranes and induces a clinical and histological profile similar to human PV when injected into neonatal mice. PVMAB786 will be a valuable tool in identifying the role of Dsg3 in epithelial cell adherence and acantholysis, mechanisms of Dsg3 processing/presentation and V gene and isotype usage in PV pathogenesis.
authors.affiliation: Department of Oral Medicine, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Yeh
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cavacini
authors.forename: Kailash C
authors.initials: KC
authors.lastname: Bhol
authors.forename: Mong-Shang
authors.initials: MS
authors.lastname: Lin
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.forename: Mark
authors.initials: M
authors.lastname: Duval
authors.forename: Marshall R
authors.initials: MR
authors.lastname: Posner
authors.forename: A Razzaque
authors.initials: AR
authors.lastname: Ahmed
mesh_terms: D000051:Acantholysis / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D015153:Blotting, Western; D051184:Desmoglein 3 / Q000276:immunology*; D018604:Epitope Mapping; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000627:therapeutic use; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D007428:Intradermal Tests; D015603:Keratinocytes; D051379:Mice; D008807:Mice, Inbred BALB C; D010392:Pemphigus / Q000276:immunology* / Q000628:therapy
chemical_list: D000911:Antibodies, Monoclonal; C071894:DSG3 protein, human; D051184:Desmoglein 3; D007074:Immunoglobulin G