Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy.
نویسندگان
چکیده
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% 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.
منابع مشابه
The Impact of Immune Response on HTLV-I in HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)
Human T lymphotropic virus type I (HTLV-I) is a retrovirus which is associated with adult T cells leukaemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a minority of HTLV-I-infected individuals. It is not clear why a minority of HTLV-I-infected individuals develop HAM/TSP and majority remains lifelong carriers. It seems that the interaction between the v...
متن کاملHTLV-1, Immune Response and Autoimmunity.
Human T-lymphotropic virus type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL). Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM) is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Sjögren's Syndrome (SS). The development of HTLV-1-driven autoimmunity is hypothesized t...
متن کاملPolymorphism in the interleukin-10 promoter affects both provirus load and the risk of human t lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis
To investigate candidate genes that influence the risk of HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), we analyzed 6 single nucleotide polymorphisms (SNP) in the interleukin-10 (IL-10) promoter region. METHODS: 280 cases of HAM/TSP patients and 255 HTLV-I seropositive asymptomatic carriers (HCs) from Kagoshima, Japan were studied. All subjects gave written informed conse...
متن کاملPolymorphism in the interleukin-10 promoter affects both provirus load and the risk of human t lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis
To investigate candidate genes that influence the risk of HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), we analyzed 6 single nucleotide polymorphisms (SNP) in the interleukin-10 (IL-10) promoter region. METHODS: 280 cases of HAM/TSP patients and 255 HTLV-I seropositive asymptomatic carriers (HCs) from Kagoshima, Japan were studied. All subjects gave written informed conse...
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ورودعنوان ژورنال:
- Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
دوره 38 2 شماره
صفحات -
تاریخ انتشار 2005