In Europe alone, autoimmune diseases that may target any body organ affect about 7% of the population. There can be up to 70 different forms of autoimmunity, among which diabetes 1 stands out as the one striking the populations of Finland, Sweden and Italy’s island of Sardinia particularly badly, for no firmly known reason.
The newest, most original approach to preventing and curing autoimmune diseases, with a specific focus on diabetes 1, is based on the major biological functions of the thymus, an organ located just behind the breastbone which is responsible for the development of T lymphocytes, the type of white blood cells ensuring cellular immunity. The 25 partners of the European consortium EURO-THYMAIDE (THYMus in AutoImmunity DEvelopment) have been working across 12 countries on this novel paradigm of the pathogenesis of autoimmunity, namely that a defect in the thymus is a major event in contributing to different autoimmune diseases.
The thymus is the site where T-cell diversity is established against the world of infectious non-self antigens, and it also programs central self-tolerance, which is the inability of T-cells to attack the components of the host. The discovery of the intrathymic expression of a great number of tissue-specific antigens has revolutionized our knowledge of the mechanisms underlying immune self-tolerance and the development of autoimmune diseases.
Professor Vincent Geneen, the coordinator of EUROTHYMAIDE, says: “It was the first international project to be centered on the thymus and the self-tolerance of the immune system. Since we know that most autoimmune diseases are linked to a dysfunction of T-lymphocites, it was very important to study the mechanism of tolerance taking place within the thymus and to show that in these diseases there is indeed a dysfunction of the tolerogenic properties of the thymus”.
Academic research groups, hospitals and SMEs within EUROTHYMAIDE have been working towards establishing a European super-laboratory with diabetes 1 as their first prototype target. As this disease can strike early on in life, one of the research topics has been about how certain viral infections may act as triggers of diabetes in children who possibly have a given combination of genes who predispose them to the condition.
“The thymus is the only organ which appeared during evolution to establish tolerance of the immune system to the self, to the body”, Professor Geneen adds. “Other studies in the world are dealing with peripheral tolerance, but we are the only ones interested in the central organ of self-tolerance, which is the thymus”. Therapeutic applications could be within sight: “Some epithelial stem cells of the thymus have been isolated and characterized, which could be very interesting for the regeneration of the thymus, in order to restore a normal functioning thymus where there is a defect triggering autoimmunity”.
If central self-tolerance is thymus-dependent and autoimmunity results from its impairment, a vaccine is needed. “We have applied for a patent to develop a vaccine against type-1 diabetes, which is based on the tolerogenic molecules that have been found in the thymus”, Professor Geneen says. “Other groups outside Europe are also trying for a vaccine, but we are the only ones working from the thymus”. A type-1 diabetes clinical trial will be part of a follow-up project. “We aim to restore stem cells to diabetes-1 patients, which may repair the thymus. For these patients, there is a destruction of the insulin-secreting beta-cells in the pancreas, and at the moment there is a lot of hope to regenerate these. However, if you can restore the beta cell mass, the immune system of the body will keep the autoimmune memory, so it’s very important to inhibit such a memory. In this way there will be no more aggression against the grafted betacells”.
This reprogramming could be done, Professor Geneen says, “by using the natural tolerogenic properties of the thymus”. The incidence of type-1 diabetes, he concludes, is about “10 new cases per 100,000 people every year, so it’s not a very frequent disease. But if you go to Finland, Sweden or Norway, the incidence is 5 times higher, although we don’t have any solid proof as to why this happens”.
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