RESUMO
There are two major clinical subsets of pemphigus vulgaris (PV)-mucosal PV (mPV) and mucocutaneous PV (mcPV). The mPV subset exhibits anti-human desmoglein (Dsg) 3 autoantibodies that fail to recognize murine Dsg3 (mDsg3); thus, passive transfer experiments of mPV IgG into wild-type (WT) mice have been unsuccessful at inducing disease. We therefore generated a fully humanized Dsg3 (hDSG3) murine model utilizing a hDsg3 transgenic animal crossed to the mDsg3 knockout line. Expression of hDsg3 in the mucosa rescues the mDsg3 knockout phenotype. Well-characterized mPV sera bind mucosal epithelia from the hDsg3 mice, but not mucosal tissues from WT mice, as detected by indirect immunofluorescence (IF). The majority of mPV sera preferentially recognize hDsg3 compared with mDsg3 by immunoprecipitation as well. Passive transfer of mPV IgG into adult hDsg3 mice, but not WT mice, induces suprabasilar acantholysis in mucosal tissues, thus confirming the pathogenicity of mPV anti-hDsg3 IgG in vivo. Human anti-hDsg3 antibodies are detected in perilesional mucosa as well as in sera of recipient mice by IF. These findings suggest that the Dsg3 epitopes targeted by pathogenic mPV IgG are human specific. This hDsg3 mouse model will be invaluable in studying the clinical transition from mPV to mcPV.
Assuntos
Desmogleína 3/genética , Imunoglobulina G/química , Pênfigo/imunologia , Animais , Autoanticorpos/química , Cromossomos Artificiais Bacterianos , Desmogleína 1/metabolismo , Desmogleína 3/metabolismo , Epitélio/metabolismo , Epitopos/química , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imunoprecipitação , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Mucosa Bucal/metabolismo , Mucosa/metabolismo , Fenótipo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Relying on a structured observation guide listing a large number of variables shown to be good predictors of aggression in bars by past researchers, trained observers spent a total of 444 hours collecting data in 25 licensed drinking establishments in Hoboken, New Jersey. Observations took place at two separate time periods, 7:30pm-10:30pm and 11:00pm-2:00am, on Thursday, Friday, and Saturday nights. Logistic regression analyses revealed the absence of bouncers and doormen as the strongest predictor of aggression in Hoboken barrooms. This is a particularly important finding considering the frequency with which bouncers and doormen are vilified in the available research on barroom aggression. Several practical prevention strategies aimed at reducing aggression in bars are proposed.