Emmanuel Mignot

Community and International Work Details

  • Project Title:  immunochip
  • Topic/emphasis:  Genetic study of many autoimmune diseases
  • Partnering Organization(s):  >100 laboratories across the world
  • Location:  International
  • This an ongoing project:  No
  • There are opportunities for student involvement in work:  No
  • Description:  Narcolepsy is common; it affects 1 person for 2000 in the general population, a frequency similar to Type I Diabetes or Multiple Sclerosis. Thanks to recent and exciting findings, there is now no doubt that narcolepsy is caused by an autoimmune destruction of 70,000 brain cells producing hypocretin, a wake producing substance. Narcolepsy is very similar to Type I Diabetes, a disease where the immune system, instead of fighting an infection, turns against one self and destroys islet cells producing insulin in the pancreas. A genetic association of narcolepsy with the human leukocyte antigen (HLA), T-cell Receptor (TCR) and other genes involved in immune regulation has been shown. Further, narcolepsy is triggered by streptococcus infections, and is associated with autoantibodies, a hallmark of autoimmune disease. In spite of these advances however, there is little research and funding in narcolepsy research; less than one thousand of the funding going to Type I Diabetes for example. This is unfortunate as narcolepsy may be the first example of a neuronal specific autoimmune disorder, and may be a model for other diseases such as schizophrenia, bipolar disorder or autism. There is increasing evidence that susceptibility to autoimmune disorders involves overlapping genetic factors. This likely explains why some people who have an autoimmune disorder are at risk for another. Using a gene scanning technique called Genome Wide Association Studies (GWAS), several hundred immune related susceptibility genes for many autoimmune disorders have been discovered (multiple sclerosis, lupus, Type I diabetes, Inflammatory Bowel syndromes, Celiac disease/Gluten intolerance, etc). In diseases where a lot of these genes have been identified, it is now possible to define general pathways of immune abnormalities that can be used to design novel therapeutics. A key to success has been the ability to survey many genes so that at the end a pathways emerge (for example IL2 and IL2R signaling in type Diabetes). The goal of the ImmunoChip project is to compare and contrast the genetic architecture of over 20 autoimmune diseases (~50,000 samples), taking advantage of results obtained in individual diseases. The Immunochip is an Illumina 200K Infinium product, with the polymorphisms chosen from autoimmune disease GWAS with significant findings. In addition, there are additional SNPs chosen to cover the HLA (from the T1DGC HLA Fine Mapping and the IMAGIN groups) and other features. The genotyping platform to be used at the University of Virginia is the Illumina BeadStation. The number of genes covered by the regional mapping is ~250. In this proposal, we are testing ~2500 narcolepsy patients at a cost of $40/sample To have these samples tested will raise narcolepsy knowledge and visibility to the level of other autoimmune diseases that are much better funded and studied. By contributing these samples to the ImmunoChip project, we will learn about the genes predisposing to narcolepsy and other autoimmune diseases. We anticipate this will increase dramatically interest and research in narcolepsy in the future. It will also lead to an understanding of what subtypes of immune pathways are disturbed in narcolepsy and maybe other autoimmune diseases, with synergic effect on the design of new therapeutic interventions.

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