RESUMO
The tropical spastic paraparesis or human T-cell lymphotropic virus associated myelopathy (TSP/HAM), has been related with an overexpression of matrix metalloproteinases (MMPs), especially MMP-9. Initial studies of reverse zymography with cerebrospinal fluid (CSF) from TSP/HAM patients, and controls showed the presence of TIMPs, endogenous MMP inhibitors. We determined in CSF the levels of TIMPs by immunoanalysis in 25 patients with TSP/HAM, and compared with two groups: controls and patients with acute and subacute inflammatory neurological diseases. We found that TIMP-2, TIMP-3 and TIMP-4 levels were significantly higher than in controls in both TSP/HAM and inflammatory patients, while TIMP-1 was increased only in the inflammatory group. Levels of MMP-3 and MMP-9 from the two groups of patients showed a significant upregulation in CSF. In the CSF of around the 70% of TSP-HAM and inflammatory patients the presence MMP-9 was detected by zymography, but not in controls. MMP-2 was only overexpressed in the acute inflammatory group. The active form of MMP-2 was observed in both groups of patients with a similar high frequency (60%). MMPs overexpressions are independent of the evolution time of the disease in TSP/HAM. The chronic overexpression of these extracelullar matrix proteins detected in CSF of TSP/HAM should be indirectly produced by secreted viral proteins being responsible for the progression of this disease, accounting for the observed differences with acute inflammatory patients. Our results support the existence of an imbalance between MMPs and their endogenous tissue inhibitors, which could be a pathogenic factor in the chronicity of TSP/HAM.
Assuntos
Infecções por Deltaretrovirus/líquido cefalorraquidiano , Metaloproteinases da Matriz/líquido cefalorraquidiano , Inibidores Teciduais de Metaloproteinases/líquido cefalorraquidiano , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Feminino , Gelatina/metabolismo , Humanos , Immunoblotting , Inflamação/líquido cefalorraquidiano , Laminina/metabolismo , Masculino , Metaloproteinase 9 da Matriz/líquido cefalorraquidiano , Pessoa de Meia-IdadeRESUMO
Tropical spastic paraparesis (TSP), a neuromyelopathy predominantly involving the pyramidal tract and commonly observed in tropical and equatorial areas, was recently found to be associated with human T lymphotropic virus type I (HTLV-I). We investigated sera and cerebrospinal fluid (CSF) from 19 patients with TSP who were from the Caribbean area, French Guiana, and Africa. Our results showed an elevated intra-blood-brain barrier IgG synthesis rate and an elevated IgG index, with an increased HTLV-I antibody-to-albumin ratio and the presence of CSF oligoclonal bands in the majority of the patients. These data, in association with similar HTLV-I antibody patterns between patients with TSP who were from these three regions, strengthen the probable etiologic role of HTLV-I in the pathogenesis of such chronic neuromyelopathies.
Assuntos
Anticorpos Antivirais/biossíntese , Infecções por Deltaretrovirus/imunologia , Deltaretrovirus/imunologia , Imunoglobulina G/biossíntese , Paralisia/imunologia , Doenças da Medula Espinal/imunologia , Adulto , Idoso , Anticorpos Antivirais/líquido cefalorraquidiano , Barreira Hematoencefálica , Côte d'Ivoire , Infecções por Deltaretrovirus/líquido cefalorraquidiano , Feminino , Guiana Francesa , Humanos , Imunoensaio , Imunoglobulina G/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular , Paralisia/líquido cefalorraquidiano , Senegal , Doenças da Medula Espinal/líquido cefalorraquidiano , Clima Tropical , Índias OcidentaisRESUMO
Three of 6 patients with spastic paraparesis in Lima, Peru, were found to have antibodies to human T-lymphotropic virus type I (HTLV-I). Blood and cerebrospinal fluid antibodies were confirmed by Western blot analysis. Multilobulated lymphocytes in blood and cerebrospinal fluid of the index case stained with monoclonal antibodies for T-helper cells and for T10, an activation marker. Blood mononuclear cells from patients with HTLV-I-associated myelopathy showed spontaneous proliferation in culture, evidence of interleukin-2 receptors, and decreased natural killer cell activity.