Neuronal molecular mimicry in immune-mediated neurologic disease Journal Article
| Authors: | Levin, M. C.; Krichavsky, M.; Berk, J.; Foley, S.; Rosenfeld, M.; Dalmau, J.; Chang, G.; Posner, J. B.; Jacobson, S. |
| Article Title: | Neuronal molecular mimicry in immune-mediated neurologic disease |
| Abstract: | 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. |
| Keywords: | immunohistochemistry; clinical article; controlled study; human tissue; human cell; cells, cultured; neurons; immunoreactivity; central nervous system; blotting, western; immune response; immunoglobulin g; antibody response; reference values; immunoblotting; parkinson disease; autoimmune diseases; multiple sclerosis; neurologic disease; htlv-i infections; human t-lymphotropic virus 1; human t cell leukemia virus; leukemia, t-cell; spastic paraplegia; brain chemistry; molecular mimicry; immune mediated injury; humans; human; priority journal; article; paraparesis, tropical spastic |
| Journal Title: | Annals of Neurology |
| Volume: | 44 |
| Issue: | 1 |
| ISSN: | 0364-5134 |
| Publisher: | Wiley Blackwell |
| Date Published: | 1998-07-01 |
| Start Page: | 87 |
| End Page: | 98 |
| Language: | English |
| DOI: | 10.1002/ana.410440115 |
| PUBMED: | 9667596 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work