title: Anti-desmoplakin antibodies in erythema multiforme and Stevens-Johnson syndrome sera: pathogenic or epiphenomenon?
abstract: The pathophysiology of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) is unclear. Whether autoantibodies against desmoplakin (Dp) I and II play a pathogenic role or result from an epitope spreading phenomenon is uncertain. Our aim was to characterize the keratinocyte antigens recognized in EM, TEN and SJS. Of 33 patients studied, 2 had TEN, 1 SJS, 9 EM major and 21 EM minor, according to Roujeau's criteria. All sera were studied by indirect immunofluorescence (IIF), immunoblotting and immunoprecipitation. Twenty normal sera were used as controls. 10/33 sera reacted with polypeptides of 215 and/or 250-kDa molecular mass, which co-migrate with Dp I and II as assessed by an anti-Dp I and II monoclonal antibody on IB. In IP, none of the anti-Dp I and -Dp II 10 patient sera immunoprecipitated Dp I and/or II from radiolabeled keratinocyte extracts. Two of 10 patient sera (SJS, EM minor) reacted with DpI and II when denaturated by the IB procedure. The reactivity against intracellular antigens DpI and II as denaturated proteins may result from the epidermal damage produced by aggressive autoreactive T cells, playing therefore only a secondary role in the pathogenesis of the disease.
authors.affiliation: University of Genoa, viale Benedetto XV, 16132, Genoa, Italy. emanuele.cozzani@unige.it
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cozzani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Zenzo
authors.forename: Valentina
authors.initials: V
authors.lastname: Calabresi
authors.forename: Marzia
authors.initials: M
authors.lastname: Caproni
authors.forename: Donatella
authors.initials: D
authors.lastname: Schena
authors.forename: Pietro
authors.initials: P
authors.lastname: Quaglino
authors.forename: Angelo V
authors.initials: AV
authors.lastname: Marzano
authors.forename: Paolo
authors.initials: P
authors.lastname: Fabbri
authors.forename: Alfredo
authors.initials: A
authors.lastname: Rebora
authors.forename: Aurora
authors.initials: A
authors.lastname: Parodi
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000032:analysis*; D051180:Desmoplakins / Q000276:immunology*; D004892:Erythema Multiforme / Q000276:immunology* / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D015603:Keratinocytes / Q000276:immunology; D010455:Peptides / Q000276:immunology; D013262:Stevens-Johnson Syndrome / Q000276:immunology* / Q000503:physiopathology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D051180:Desmoplakins; D010455:Peptides