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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1998-7-22
|
| pubmed:abstractText |
Molecular mimicry is implicated in the pathogenesis of autoimmune diseases such as diabetes mellitus, rheumatoid arthritis, and multiple sclerosis (MS). Cellular and antibody-mediated immune responses to shared viral-host antigens have been associated with the development of disease in these patients. Patients infected with human T-lymphotropic virus type I (HTLV-I) develop HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an immune-mediated disorder of the central nervous system (CNS) that resembles some forms of MS. Damage to neuronal processes in the CNS of HAM/TSP patients is associated with an activated cellular and antibody-mediated immune response. In this study, IgG isolated from HAM/TSP patients was immunoreactive with uninfected neurons and this reactivity was HTLV-I specific. HAM/TSP IgG stained uninfected neurons in human CNS and cell lines but not nonneuronal cells. Neuronal western blots showed IgG reactivity with a single 33-kd band in all HAM/TSP patients tested. By contrast, no neuron-specific IgG reactivity could be demonstrated from HTLV-I seronegative controls and, more important, from HTLV-I seropositive, neurologically asymptomatic individuals. Both immunocytochemical staining and western blot reactivity were abolished by preincubating HAM/TSP IgG with HTLV-I protein lysate but not by control proteins. Staining of CNS tissue by a monoclonal antibody to HTLV-I tax (an immunodominant HTLV-I antigen) mimicked HAM/TSP IgG immunoreactivity. There was no staining by control antibodies. Absorption of HAM/TSP IgG with recombinant HTLV-I tax protein or preincubation of CNS tissue with the monoclonal antibody to HTLV-I tax abrogated the immunocytochemical and western blot reactivity of HAM/TSP IgG. Furthermore, in situ human IgG localized to neurons in HAM/TSP brain but not in normal brain. These data indicate that HAM/TSP patients develop an antibody response that targets uninfected neurons, yet reactivity is blocked by HTLV-I, suggesting viral-specific autoimmune reactivity to the CNS, the damaged target organ in HAM/TSP.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0364-5134
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
44
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
87-98
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:9667596-Autoimmune Diseases,
pubmed-meshheading:9667596-Blotting, Western,
pubmed-meshheading:9667596-Brain Chemistry,
pubmed-meshheading:9667596-Cells, Cultured,
pubmed-meshheading:9667596-HTLV-I Infections,
pubmed-meshheading:9667596-Human T-lymphotropic virus 1,
pubmed-meshheading:9667596-Humans,
pubmed-meshheading:9667596-Immunoglobulin G,
pubmed-meshheading:9667596-Immunohistochemistry,
pubmed-meshheading:9667596-Leukemia, T-Cell,
pubmed-meshheading:9667596-Molecular Mimicry,
pubmed-meshheading:9667596-Neurons,
pubmed-meshheading:9667596-Paraparesis, Tropical Spastic,
pubmed-meshheading:9667596-Parkinson Disease,
pubmed-meshheading:9667596-Reference Values
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Neuronal molecular mimicry in immune-mediated neurologic disease.
|
| pubmed:affiliation |
Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD, USA.
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| pubmed:publicationType |
Journal Article
|