title: Cicatricial pemphigoid with circulating autoantibodies to beta4 integrin, bullous pemphigoid 180 and bullous pemphigoid 230.
abstract: Cicatricial pemphigoid is a heterogeneous group of autoimmune subepidermal blistering diseases associated most commonly with autoantibodies to bullous pemphigoid (BP)180 and less frequently with those to laminin 5 or type VII collagen. In addition, a few cases have been described with autoantibodies to the beta4 subunit of alpha6beta4 integrin. We describe a patient with extensive disease of ocular, oral, pharyngeal, laryngeal and genital mucous membranes that healed with scarring of conjunctivae. IgG autoantibodies bound to the dermal-epidermal junction on direct immunofluorescence (IF) microscopy and to the epidermal side of 1 mol L(-1) NaCl-split skin on indirect IF microscopy. Our patient's circulating IgG recognized a 205-kDa protein in extracts of 293T cells transfected with the beta4 subunit of alpha6beta4 integrin and in the cell extract of DJM-1 cells. Our patient's IgG and IgA autoantibodies also reacted with full-length BP180 derived from epidermal extracts and the ectodomain of BP180 (LAD-1) derived from culture supernatant of keratinocytes. In addition, a weak IgG reaction with BP230 was noted. The disease rapidly responded to dexamethasone-cyclophosphamide pulse therapy, and immunoblot reactivity to both beta4 integrin and BP180 decreased according to disease activity.
authors.affiliation: Department of Dermatology, University of Würzburg, Germany. leverkus-m.derma@mail.uni-wuerzburg.de
authors.forename: M
authors.initials: M
authors.lastname: Leverkus
authors.forename: K
authors.initials: K
authors.lastname: Bhol
authors.forename: Y
authors.initials: Y
authors.lastname: Hirako
authors.forename: H
authors.initials: H
authors.lastname: Pas
authors.forename: C
authors.initials: C
authors.lastname: Sitaru
authors.forename: G
authors.initials: G
authors.lastname: Baier
authors.forename: E B
authors.initials: EB
authors.lastname: Bröcker
authors.forename: M F
authors.initials: MF
authors.lastname: Jonkman
authors.forename: A R
authors.initials: AR
authors.lastname: Ahmed
authors.forename: D
authors.initials: D
authors.lastname: Zillikens
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D002352:Carrier Proteins; D003094:Collagen / Q000276:immunology; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D039663:Integrin beta4; D008297:Male; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010390:Pemphigoid, Benign Mucous Membrane / Q000276:immunology*; D000097805:Collagen Type XVII
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D039663:Integrin beta4; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human