Autoimmunity due to molecular mimicry as a cause of neurological disease
| Autor: | Joseph C. Callaway, Karen A. Hasty, John M. Stuart, Franck Kalume, F. Curtis Dohan, Michael C. Levin, Sangmin Lee, Yvette Morcos, Joseph R. Zunt, Dominic M. Desiderio |
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| Rok vydání: | 2002 |
| Předmět: |
DNA
Complementary Patch-Clamp Techniques Heterogeneous Nuclear Ribonucleoprotein A1 Autoimmunity Cross Reactions medicine.disease_cause Heterogeneous-Nuclear Ribonucleoproteins Article General Biochemistry Genetics and Molecular Biology Immune system Antigen immune system diseases Heterogeneous-Nuclear Ribonucleoprotein Group A-B Tropical spastic paraparesis medicine Humans RNA Messenger Autoimmune disease Human T-lymphotropic virus 1 Systemic lupus erythematosus biology Reverse Transcriptase Polymerase Chain Reaction Molecular Mimicry Antibodies Monoclonal Brain virus diseases General Medicine medicine.disease HTLV-I Infections Virology Molecular mimicry Ribonucleoproteins Organ Specificity Immunoglobulin G Immunology biology.protein Nervous System Diseases Antibody |
| Zdroj: | Nature Medicine. 8:509-513 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm0502-509 |
| Popis: | One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease1,2. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS)1–4. There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5–7). HAM/TSP patients develop antibodies to neurons8. We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5,9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged7. Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS. |
| Databáze: | OpenAIRE |
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