HTLV-1 infection cause abnormalities in the immunological response characterized by spontaneous T cell proliferation and production of high levels of pro-inflammatory (IFN-gamma and TNF-alpha) cytokines. The myelopathy associated to HTLV-1 (HAM/TSP) and acute T cell leukemia are the most important diseases related to HTLV-1 and the pathogenesis of these diseases are associated with abnormalities in the T cell response. However while abnormalities in T cell responses are found in a large percentage of individuals infected with HTLV-1, HAM/TSP is documented in less than 5% of the infected individuals. The major hypothesis of this application is that clinical, neurological and immunological abnormalities occur in higher frequency than previously described in HTLV-1 infected patients. The major aim of this application is to identify early, clinical and immunological markers of disease in HTLV-1 infected individuals.
The aim 1 is to identify clinical manifestations associated to HTLV-I. This will be performed analyzing the clinical data that has been generated in the last 5 years and compared with blood donors not infected with HTLV-1 in a case control study.
The aim 2 will determine by sophisticated complementary exams if HTLV-1 carriers who have immunological abnormalities similar to that observed in HAM/TSP will have early evidence of neurological involvement. This will be tested in a case control study comparing the neurological findings, cytokine levels in cerebral spinal fluid and magnetic resonance imaging in HTLV-1 carriers who have high levels of IFN-gamma and lack of modulation of IFN-gamma production, similar to that observed in HAM/TSP, with HTLV-1 carriers who have no or mild alterations in their immunological responses. Results of these studies will contribute to identify clinical and neurological manifestations associated with HTLV-1, which can be confirmed in the future by a longitudinal study in the natural history of disease and will shed light on future more effective and earlier therapeutic interventions to this disease.
| Caskey, Marina F; Morgan, Daniel J; Porto, Aurelia F et al. (2007) Clinical manifestations associated with HTLV type I infection: a cross-sectional study. AIDS Res Hum Retroviruses 23:365-71 |
| Morgan, Daniel J; Caskey, Marina F; Abbehusen, Cristiane et al. (2007) Brain magnetic resonance imaging white matter lesions are frequent in HTLV-I carriers and do not discriminate from HAM/TSP. AIDS Res Hum Retroviruses 23:1499-504 |
| Santos, Silvane B; Porto, Aurelia F; Muniz, Andre Luiz et al. (2006) Modulation of T cell responses in HTLV-1 carriers and in patients with myelopathy associated with HTLV-1. Neuroimmunomodulation 13:145-51 |
| Guerreiro, J B; Santos, S B; Morgan, D J et al. (2006) Levels of serum chemokines discriminate clinical myelopathy associated with human T lymphotropic virus type 1 (HTLV-1)/tropical spastic paraparesis (HAM/TSP) disease from HTLV-1 carrier state. Clin Exp Immunol 145:296-301 |
