Grant: Project Grant

Autoimmune disease happens when some T-lymphocytes, cells of the immune system, attack and destroy organs of the body, e.g. the insulin-producing cells in the pancreas (type 1 diabetes) or the lining of the intestine (celiac disease). Most T-lymphocytes in the blood of a patient perform normally their task, which is to attack and destroy bacteria, viruses and other non-self substances. This requires the ability to distinguish between self and non-self. Why do most lymphocytes of a patient retain this ability and only a tiny fraction (less than 1%) loses it and causes disease? To answer this question, we will isolate these few rogue cells and will examine their DNA to see how it has changed in the cellular process of maturing from bone marrow precursors to fully functional lymphocytes with specificity for attacking a body part. We will look for genes that have independently undergone such alterations in different patients, as the most likely to be involved in the autoimmune process. We aim to develop diagnostic tests that will be used to categorize patients according to which genes are affected, based on which they may respond optimally to different treatments (precision medicine). Development of novel therapeutics targeting the genes involved is the final objective.