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EURO-THYMAIDE — Result In Brief

Project ID: 503410
Country: Belgium

The threshold of self-tolerance and autoimmune disease

Dysfunction of an insignificant looking organ behind the breast bone, the thymus, is heavily implicated in autoimmune disease. An EU-funded project, EURO-Thymaide has explored the mechanics of self-tolerance at the molecular level.
The threshold of self-tolerance and autoimmune disease
Promiscuous gene expression (pGE) is at the root of immunological self-tolerance. Thymus epithelial cells commonly express tissue-specific genes in a promiscuous manner. Genetic defects in the tolerance mechanism results in autoimmune diseases like diabetes, rheumatoid arthritis (RA) and multiple sclerosis. T-cells that attack the body's own proteins are eliminated in the thymus.

Based on knowledge of thymus-dependent self-tolerance, the EU-funded project EURO-Thymaide aimed to develop innovative strategies for diagnosis and treatment of Type 1 diabetes (T1D). In particular, the researchers focused on the role of a particular gene, autoimmune regulator (AIRE).

The AIRE gene produces a protein that controls and or influences T-cell deletion and migration and antigen presentation. When AIRE is defective, T-cells can attack the body resulting in an autoimmune situation.

Studies on the role of pGE in T1D and two other autoimmune conditions, myasthenia gravis and Graves' thyroiditis, have revealed that genetic polymorphisms in the regions are responsible for regulation of target self-antigens. This phenomenon sets a threshold for self-tolerance beyond which there is predisposition to disease.

Project success came in extension of the patent for the thymus-based tolerogenic vaccine for T1D and subsequent delivery in Australia. Applications were made for another two patents and one technological application, and a diagnostic test was developed for commercial use. EURO-Thymaide partners were also involved in another research initiative to detect T-cells specific for auto-immune related antigens, an application that can be used to evaluate T-cell immunity in disease.

Applications for the many promising deliverables of EURO-Thymaide are many and include the development of new therapies for autoimmune diseases, infectious diseases and cancer.

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