Researchers from the CiMUS of the USC propose a paradigm shift to understand the origin of type 1 diabetes.

• The study, led by the researcher Iria Gómez Touriño, advances in the knowledge of the mechanisms that cause this disease, using novel molecular and sequencing techniques.
• The work, the focus of one of the most competitive international projects in the field of type 1 diabetes, proposes an alternative explanation for the causes underlying the auto-immune process that characterises this pathology.

The causes of type 1 diabetes, an autoimmune disease with a high incidence, expected to increase by 66% by 2040, are still poorly understood. To date, insulin injection is the only effective treatment administered; and T-lymphocytes, a type of white blood cell, the reason that triggers it according to scientific evidence. Now, researchers at the USC CiMUS, led by Iria Gómez Touriño, suggest a new line that represents a paradigm shift in the approach to the disease, focusing on new molecular mechanisms and based on novel techniques such as high-throughput screening or bioinformatics tools.

This work, which will be carried out at the CiMUS of the USC, is possible thanks to the Juvenile Diabetes Research Foundation (JDRF) of the USA, through the granting to Iria Gómez Touriño of one of the most competitive international calls for proposals in the field of type 1 diabetes (Career Development Award). The JDRF will provide nearly $1,000,000 over the next 5 years to fund this research project. This type of project is aimed at attracting and consolidating the careers of young researchers with high potential in the field of diabetes. In fact, the grant awarded to Iria Gómez Touriño, similar in magnitude to the Starting Grants of the European Research Council (ERC), is one of three currently active in Europe.

A highly disabling chronic disease that reduces quality of life and life expectancy.

Type 1 diabetes (T1D1) is an autoimmune disease in which our immune system destroys the cells in the pancreas that produce insulin. This causes the patient to have very low or no insulin levels and so glucose cannot enter their cells, causing serious damage that can lead to death if the disease is not diagnosed and treated. T1D occurs mainly in children and young adults. It is a chronic condition that greatly diminishes quality of life, especially in young children who have to learn to control their blood glucose levels on a daily basis, as well as causing long-term complications such as retinal and kidney damage and reduced life expectancy, at great cost to both patients and healthcare systems.

The only treatment at present is insulin injection, although a drug has recently been approved for people in pre-diabetic stages. The incidence of TD1 is increasing, especially in more developed countries, and is expected to increase by 66% by 2040. "Unfortunately, we still don't know why. We also don't understand why the disease occurs, or why the immune system attacks only those insulin-producing cells, the beta cells. We know that it is due to a combination of genetic and environmental factors, but we don't know them completely," says USC CiMUS researcher Iria Gómez Touriño.

Objective: to learn more about its origin and open the door to new treatments.

The current dogma, evidenced by a large number of studies, is that it is T-lymphocytes, a type of white blood cell, that mistakenly recognise beta cells as foreign and proceed to eliminate them. These lymphocytes have receptors, scanners, which identify proteins and fats (antigens) on the cells, and decide whether these antigens are from the person or are foreign (from viruses, bacteria, etc.). In fact, some current experimental treatments are based on injecting these antigens to convince the immune system that it does not have to attack them. However, it seems that not only proteins and fats can be antigens recognised by the immune system.

"We propose that one type of these very specific yet aggressive lymphocytes can recognise substances derived from the metabolism of beta cells. In other words, a beta cell that is stressed, infected or has a genetic defect could behave abnormally, producing metabolites that these aggressive immune cells could recognise, killing the beta cells in a short time. This represents a paradigm shift," says Iria Gómez Touriño, in the approach to type 1 diabetes. "Moreover, preliminary data from our and other groups suggest that it could explain the onset of the disease," she explains.

Access to more than 600 patient samples from all over Europe

To test this, the CiMUS group will use novel techniques (metabolomics, high-throughput screening, flow cytometry, bioinformatics and single cell sequencing) on cell lines and blood cells from patients, family members without the disease and healthy people to see what these cells are like and what antigens they recognise. This would open the door to the development of new antigen-specific immunotherapies that would be more universal than those based on protein antigens, as well as advancing our knowledge of the underlying causes of this disease. The USC team will collect blood samples from Galician patients, through the endocrinology services of the hospitals of Santiago and A Coruña, and will also have access to a large biobank of cells from patients and their relatives in the rest of Europe through INNODIA, a global platform made up of more than 30 academic institutions, seven industrial partners and two patient organisations that pool their knowledge and experience to fight type 1 diabetes. In total, 600 samples from across Europe.

Iria Gómez Touriño is a CiMUS researcher and professor at the USC, as well as being linked to the Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS). With a PhD in molecular biology, she has worked in laboratories in the United Kingdom, Germany and Spain and has received several grants and awards throughout her research career, including two Marie Curie contracts from the European Union. The Career Development Award is a new boost to the consolidation of her team's line of research.