A Breakthrough in Understanding Autoimmune Disease Genetics

June 10, 2024

There is a specific region on chromosome 21 known as chr21q22 that has been associated with the development of five autoimmune diseases: inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis, and Takayasu’s arteritis. Until recently, the exact gene in this area responsible for this increased susceptibility and its mechanism were unknown.A Nature paper titled “A disease-associated gene desert directs macrophage inflammation through ETS2” identified the gene and potential mechanism for this association.

In this study scientists identified that the gene on chromosome 21 responsible is ETS2. They then determined that it regulates a type of immune cell that promotes inflammation known as the inflammatory macrophage. When they increased the amount of ETS2 made in macrophages they were able to reproduce the type of inflammation seen in autoimmune diseases. This provides evidence that this association is contributing to disease development in patients.

This is a major discovery because it helps us better understand why some people are genetically predisposed to developing certain autoimmune diseases. It also gives us a clear target for drug development that may help us better treat patients with these diseases.

Citation:

Stankey, C.T., Bourges, C., Haag, L.M. et al. A disease-associated gene desert directs macrophage inflammation through ETS2. Nature 630, 447–456 (2024). https://doi.org/10.1038/s41586-024-07501-1