The pathogenesis of tropical spastic paraparesis/human T-cell leukemia type I-associated myelopathy.
Tropical spastic paraparesis/human T-cell leukemia type I-associated myelopathy (TSP/HAM) is caused by a human T-cell leukemia virus type I (HTLV-I) after a long incubation period. TSP/HAM is characterized by a chronic progressive paraparesis with sphincter disturbances, no/mild sensory loss, the absence of spinal cord compression and seropositivity for HTLV-I antibodies. The pathogenesis of this entity is not completely known and involves a multivariable phenomenon of immune system activation against the presence of HTLV-I antigens, leading to an inflammatory process and demyelination, mainly in the thoracic spinal cord. The current hypothesis about the pathogenesis of TSP/HAM is: 1) presence of HTLV-I antigens in the lumbar spinal cord, noted by an increased DNA HTLV-I load; 2) CTL either with their lytic functions or release/production of soluble factors, such as CC-chemokines, cytokines, and adhesion molecules; 3) the presence of Tax gene expression that activates T-cell proliferation or induces an inflammatory process in the spinal cord; 4) the presence of B cells with neutralizing antibody production, or complement activation by an immune complex phenomenon, and 5) lower IL-2 and IFN-gamma production and increased IL-10, indicating drive to a cytokine type 2 pattern in the TSP/HAM subjects and the existence of a genetic background such as some HLA haplotypes. All of these factors should be implicated in TSP/HAM and further studies are necessary to investigate their role in the development of TSP/HAM.
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Instituto de Moléstias Infecciosas Emílio Ribas, São Paulo, SP, Brasil. j31@hotmail.com
Penalva-de-Oliveira
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D016207:Cytokines / Q000096:biosynthesis; D004279:DNA, Viral / Q000276:immunology; D015485:Deltaretrovirus Antigens / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000821:virology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016662:Virus Integration
D016207:Cytokines; D004279:DNA, Viral; D015485:Deltaretrovirus Antigens