RESUMEN
Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease of the skin and mucous membranes, characterized by autoantibodies against type VII collagen (COL7), a major component of anchoring fibrils. Different clinical EBA phenotypes are described, including mechanobullous and inflammatory variants. Most EBA patients' sera react with epitopes located within the non-collagenous 1 (NC1) domain of human COL7. However, it has remained unclear whether antibody binding to these different epitopes is pathogenically relevant. To address this issue, we generated recombinant proteins covering the entire NC1 domain. IgG reactivity with these proteins was analyzed in sera of 69 EBA patients. Most recognized clusters of epitopes throughout the NC1 domain. No correlation was detected between antibody specificity and clinical phenotype. To study the pathogenicity of antibodies specific to different NC1 subdomains, rabbit antibodies were generated. All these antibodies caused dermal-epidermal separation ex vivo. Antibodies against two of these subdomains were injected into mice carrying null mutations of mouse COL7 and the human COL7 transgene and induced subepidermal blisters. We here document that autoantibodies to COL7, independent of the targeted epitopes, induce blisters both ex vivo and in vivo. In addition, using COL7-humanized mice, we provide in vivo evidence of pathogenicity of autoantibodies binding to human COL7.
Asunto(s)
Autoanticuerpos/química , Vesícula/metabolismo , Colágeno Tipo VII/química , Epidermólisis Ampollosa Adquirida/metabolismo , Epítopos/química , Animales , Anticuerpos/química , Autoanticuerpos/inmunología , Dermis/metabolismo , Epidermis/metabolismo , Femenino , Humanos , Inmunoglobulina G/química , Inflamación , Masculino , Ratones , Ratones Transgénicos , Mutación , Estructura Terciaria de Proteína , Conejos , Proteínas Recombinantes/química , TransgenesRESUMEN
UNLABELLED: Sinistrality characterized by an excess of non-right handedness has been reported in schizophrenic patients. Two factors, sex and kind of evaluation of handedness have contributed to major discrepancies across studies. AIM: The hypothesis tested was that schizophrenic patients show a sinistral shift in handedness compared to controls taking into account the sex and using a continuum scoring system for evaluating handedness. METHODS: Seventy-three (73.1% males) schizophrenic patients (DSMIV) and 81 (64.2% males) controls were evaluated with the Edinburgh Handedness Inventory (EHI [Neuropsychologia, 9 (1971) 97]). RESULTS: The EHI score mean difference between patients with schizophrenia and control group was not significant when sex was taken into account. CONCLUSION: Schizophrenic patients taken as a whole did not show a sinistral shift in handedness even if the sex and the continuum score for handedness were considered.