Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy.
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.
García-Vallejo
F
F
Laboratorio de Biología Molecular y Patogénesis, Departamento de Ciencias Fisiológicas, Facultad de Ciencias da Saude, Universidad del Valle, Cali, Colombia. fegarva@telesat.com.co
Domínguez
M C
MC
Tamayo
O
O
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001253:Astrocytes / Q000276:immunology / Q000821:virology*; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D015153:Blotting, Western; D003429:Cross Reactions; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D018716:Molecular Mimicry / Q000276:immunology*; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D001323:Autoantibodies