Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy

Viruses share antigenic sites with normal host cell components, a phenomenon known as molecular mimicry. It has long been suggested that viral infections might trigger an autoimmune response by several mechanisms including molecular mimicry. More than 600 antiviral monoclonal antibodies generated against 11 different viruses have been reported to react with 3.5 percent of cells specific for uninfected mouse organs. The main pathological feature of tropical spastic paraparesis/human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (TSP/HAM) is a chronic inflammation of the spinal cord characterized by perivascular cuffing of mononuclear cells accompanied by parenchymal lymphocytic infiltration. We detected the presence of autoantibodies against a 98- to 100-kDa protein of in vitro cultured human astrocytes and a 33- to 35-kDa protein from normal human brain in the serum of HTLV-I-seropositive individuals. The two cell proteins exhibited molecular mimicry with HTLV-I gag and tax proteins in TSP/HAM patients, respectively. Furthermore, the location of 33- to 35-kDa protein cross-reaction correlated with the anatomical spinal cord areas (in the rat model) in which axonal damage has been reported in several cases of TSP/HAM patients. Our experimental evidence strongly suggests that the demyelinating process occurring in TSP/HAM may be mediated by molecular mimicry between domains of some viral proteins and normal cellular targets of the spinal cord sections involved in the neurodegeneration.

Localización histoquímica e inmunohistoquímica de fibrocitos en la cóclea de la rata / Histochemical and immunohistochemical location of fibrocyts in the cochlea of rats

El fibrocito, célula de origen mesenquimal del ligamento espiral de la coclea, ha sido investigado usando tecnicas inmunohistoquimicas que al intentar reproducirlas fallan debido a la impredecible alteracion de sitios antigenicos introducidos durante el procesamiento de la muestra. El presente estudio describe la estandarizacion de una tecnica histoquimica e inmunohistoquimica para la localizacion del fibrocito en la coclea de la rata. Dos ejemplares, bajo anestesia general con nembutal recibieron una inyeccion intracardiaca de fijadores tipo aldehidos, buffer salino fosfato y sales precipitantes. Luego de la muerte del animal su cabeza se sometio a postfijacion y decalcificacion, para realizarle cortes con microtomo cada 5 micrometros y tincion cada decima placa con hematoxilina-eosina. Finalmente, se utilizó inmunohistoquimica indirecta con el metodo Avidina-biotina conjugada y marcador monoclonal anti-vimentina y la proteina S100, lográndose la identificacion de los fibrocitos y demás componentes del organo de corti murino. La estandarizacion de esta tecnica es un hecho trascendental para el proceso de investigacion histopatologica del oido interno, aplicable al estudio de patologias que afecten a los fibrocitos del ligamento espiral