title: Bullous pemphigoid and linear IgA dermatosis sera recognize a similar 120-kDa keratinocyte collagenous glycoprotein with antigenic cross-reactivity to BP180.
abstract: Circulating IgG from a large subset of bullous pemphigoid (BP) patients reacted on immunoblot with a 120-kDa protein in conditioned keratinocyte culture medium and in keratinocyte cell extracts. A protein with a similar molecular weight was recognized by circulating IgA from a subset of patients with linear IgA dermatosis (LAD). Both affinity-purified 120-kDa-specific BP IgG and 120-kDa-specific LAD IgA bound to the roof of salt-split skin. Both proteins recognized are collagenous glycoproteins. Deglycosylation with N-glycosidase F resulted in an identical reduction in molecular weight for both the BP-IgG-recognized protein and the LAD-IgA-recognized protein. Both proteins were equally susceptible to digestion with type VII collagenase. Furthermore, both proteins were absent from conditioned culture medium of keratinocytes from patients with BP180-deficient general atrophic benign epidermolysis bullosa (GABEB). Immunodepletion studies showed that the 120-kDa LAD antigen could be removed from conditioned culture medium by anti-120-kDa BP IgG. Thus these results indicate that these proteins are either highly related or, most probably, identical. A strong antigenic relationship between the 120-kDa protein and the 180-kDa bullous pemphigoid antigen (BP180) was detected by cross-reaction of affinity-purified anti-120-kDa BP patient antibodies to BP180 and cross-reaction of monoclonal anti-180-kDa antibodies to the 120-kDa protein. Notwithstanding this cross-reactivity, the 120-kDa protein also exhibits unique epitopes demonstrated by the nonreactivity of individual anti-120-kDa BP and LAD patient serum with the 180-kDa antigen.
authors.affiliation: Department of Dermatology, University Hospital, Groningen, The Netherlands.
authors.forename: H H
authors.initials: HH
authors.lastname: Pas
authors.forename: G J
authors.initials: GJ
authors.lastname: Kloosterhuis
authors.forename: K
authors.initials: K
authors.lastname: Heeres
authors.forename: J B
authors.initials: JB
authors.lastname: van der Meer
authors.forename: M F
authors.initials: MF
authors.lastname: Jonkman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000276:immunology*; D002675:Child, Preschool; D002846:Chromatography, Affinity; D003094:Collagen / Q000378:metabolism; D003429:Cross Reactions; D017077:Culture Media, Conditioned / Q000737:chemistry; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D015603:Keratinocytes / Q000737:chemistry*; D008875:Middle Aged; D009154:Mutation; D010391:Pemphigoid, Bullous / Q000097:blood* / Q000276:immunology*; D011485:Protein Binding; D012871:Skin Diseases / Q000097:blood*
chemical_list: D000954:Antigens, Surface; D017077:Culture Media, Conditioned; D000939:Epitopes; D006023:Glycoproteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D003094:Collagen