Immunological Response and Disease Expression in HTLV-1

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DESCRIPTION (provided by applicant): 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.