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Pathophysiology, genetics and immunology of narcolepsy| old_uid | 17141 |
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| title | Pathophysiology, genetics and immunology of narcolepsy |
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| start_date | 2019/01/21 |
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| schedule | 11h-12h |
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| online | no |
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| details | Conférence prestige |
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| summary | Type 1 narcolepsy (T1N0) is caused by the loss of 20,000 hypothalamic neurons containingthewakepromotingpeptidehypocretin/orexin. Genetic,epidemiological and immunological studies indicate that the loss of these neurons is of autoimmune origin. The most common trigger of the autoimmune process is likely influenza-A (and in rare cases vaccination). Specific hemagglutinin sequences, when bound to DQ0602, an HLA subtype present in 97% of cases (vs 25% of controls), can trigger the recruitment of specific CD4 T cells that are critical to hypocretin cell loss. These T cells carry specific TCR sequences that are marked by QTL and narcolepsy association studies. Our results provide evidence for autoimmunity and molecular mimicry with flu antigens modulated by genetic components in the pathophysiology of T1N. Because of its simpler pathophysiology. narcolepsy is likely the first autoimmune disease that will have its pathophysiology largely understood through GWAS analysis and associated functional studies. Novel diagnostic markers are also likely to result, and treatment of the disease with hypocretin/orexin agonist is now under investigation. |
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| responsibles | Oliviero |
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