RESUMO
Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected allergen-blocking monoclonal IgG antibodies against the immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the allergic response in mice and in cat-allergic patients: a single dose of blocking IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p = 0.0003), with a magnitude observed at day 8 similar to that reported with years of conventional SIT. This study suggests that simply augmenting the blocking IgG/IgE ratio may reverse allergy.
Assuntos
Anticorpos Monoclonais/farmacologia , Dessensibilização Imunológica/métodos , Glicoproteínas/imunologia , Hipersensibilidade/terapia , Imunoglobulina G/farmacologia , Receptores de IgE/imunologia , Adolescente , Adulto , Alérgenos/administração & dosagem , Alérgenos/imunologia , Alérgenos/isolamento & purificação , Pelo Animal/química , Pelo Animal/imunologia , Animais , Anticorpos Monoclonais/biossíntese , Ligação Competitiva , Gatos , Misturas Complexas/química , Misturas Complexas/imunologia , Modelos Animais de Doenças , Feminino , Glicoproteínas/administração & dosagem , Glicoproteínas/isolamento & purificação , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/fisiopatologia , Imunoglobulina E/química , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Imunoglobulina G/biossíntese , Masculino , Camundongos , Pessoa de Meia-Idade , Ligação Proteica/efeitos dos fármacos , Receptores de IgE/química , Receptores de IgE/metabolismoRESUMO
A case of a spinal artery aneurysm is presented and the relevant literature is reviewed. The pathology of this aneurysm differed from that of standard intracranial aneurysms. The coexistence of a spinal aneurysm and fibromuscular hyperplasia has not been previously reported.
Assuntos
Aneurisma/patologia , Medula Espinal/irrigação sanguínea , Aneurisma/complicações , Aneurisma/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Feminino , Displasia Fibromuscular/complicações , Displasia Fibromuscular/patologia , Humanos , Pessoa de Meia-Idade , Radiografia , Artéria Renal/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Hemorragia Subaracnóidea/etiologiaRESUMO
Two cases of painful posttraumatic scaphoid malunion (hump-back deformity) associated with dorsal intercalated segmental instability deformity and limitation of wrist motion are presented. Carpal alignment and wrist motion improved after an experimental opening wedge scaphoid osteotomy with iliac bone graft and Herbert screw fixation. The scaphoid deformities (angulation and shortening) were effectively corrected.