RESUMEN
Hemitruncus arteriosus is a rare congenital deformity that results in early infant mortality. Persistence into adulthood is very unusual and is associated with pulmonary hypertension. We report a case in an adult male with the associated clinical issues.
RESUMEN
Multiple Sclerosis is an autoimmune disease directed against myelin proteins. The etiology of MS is poorly defined though, with no definitive causative agent yet identified. It has been hypothesized that MS may be a multifactorial disease resulting in the same end product: the destruction of myelin by the immune system. In this report we describe a potential role for heat shock proteins in the pathogenesis of MS. We isolated Hsp70 from the normal appearing white matter of both MS and normal human brain and found this was actively associated with, among other things, immunodominant MBP peptides. Hsp70-MBP peptide complexes prepared in vitro were shown to be highly immunogenic, with adjuvant-like effects stimulating MBP peptide-specific T cell lines to respond to normally sub-optimal concentrations of peptide. This demonstration of a specific interaction between Hsp70 and different MBP peptides, coupled with the adjuvanticity of this association is suggestive of a possible role for Hsp70 in the immunopathology associated with MS.
Asunto(s)
Autoantígenos/inmunología , Química Encefálica , Epítopos de Linfocito T/inmunología , Proteínas HSP70 de Choque Térmico/inmunología , Epítopos Inmunodominantes/inmunología , Esclerosis Múltiple/inmunología , Vaina de Mielina/química , Proteínas del Tejido Nervioso/inmunología , Fragmentos de Péptidos/inmunología , Especificidad del Receptor de Antígeno de Linfocitos T , Factores de Transcripción/inmunología , Adyuvantes Inmunológicos , Secuencia de Aminoácidos , Autoantígenos/química , Autoantígenos/aislamiento & purificación , Línea Celular , Epítopos de Linfocito T/química , Epítopos de Linfocito T/aislamiento & purificación , Proteínas HSP70 de Choque Térmico/química , Proteínas HSP70 de Choque Térmico/aislamiento & purificación , Humanos , Epítopos Inmunodominantes/química , Epítopos Inmunodominantes/aislamiento & purificación , Inmunoprecipitación , Datos de Secuencia Molecular , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/patología , Proteína Básica de Mielina , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/aislamiento & purificación , Fragmentos de Péptidos/química , Fragmentos de Péptidos/aislamiento & purificación , Mapeo de Interacción de Proteínas , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Linfocitos T/inmunología , Factores de Transcripción/química , Factores de Transcripción/aislamiento & purificaciónRESUMEN
Multiple Sclerosis (MS) is a chronic inflammatory disease of the CNS which is characterized by large mononuclear cell infiltration and significant demyelination. CXCL8 is a chemo-attractant for both neutrophils and monocytes and triggers their firm adhesion to endothelium. In this study, we demonstrate that serum CXCL8 and CXCL8 secretion from PBMCs are significantly higher in untreated MS patients compared to controls and are significantly reduced in MS patients receiving interferon-beta1a therapy. We suggest that CXCL8 may serve as a marker of monocyte activity in MS and may play a role in monocyte recruitment to the CNS.