TIMID focuses on aberrant immune responses that play a role in diseases such as type 1 diabetes, Crohn’s and Ulcerative Colitis, Spondylosing Arthritis, and the transplant rejection disease known as “graft vs. host disease”. The main problem of these immune-mediated inflammatory diseases (IMIDs) is that the disease can vary greatly from patient to patient and as a result is difficult to treat. There are strong indications that these IMID share common disease mechanisms. The TIMID research is aimed at making a new classification (taxonomy) of these inflammatory diseases on the basis of the immunological profile that arises from a certain aberrant immune response. By making a new classification, the researchers aim to find common denominators with which they can better predict which treatment works for which patient.
Graphic summary of the TIMID research project
Our immune system protects us against pathogens such as bacteria and viruses. Once we have been in contact with a pathogen, we are then protected, we are immune. This is the principle of vaccination. Cancer is caused by derailed body cells that also attacks the immune system. We simply cannot live without a properly functioning immune system. Sometimes the immune system makes a mistake and attacks its own body, and that has very nasty consequences. For example, with type 1 diabetes, the immune system attacks the pancreas and with rheumatism it attacks the joints. There are many other diseases in which the immune system plays a crucial role. Celiac disease, for example, where the immune system reacts against innocent gluten proteins, and Crohn’s disease, where a defense reaction against the gut microbes leads to inflammation in the gut.
Immune reactions are also involved in the development and maintenance of various skin disorders, colon cancer and rejection reactions after stem cell transplantation. All of these diseases are therefore referred to as “immune mediated inflammatory diseases”, abbreviated as IMID. The major problem with IMID is that the disease can vary greatly from patient to patient and is therefore difficult to treat. The number of people with IMID is rising sharply. Our lifestyle plays a major role in this. Better hygiene and changing eating habits have a major influence on the composition of our gut microbes. As long as the immune system and the intestinal microbes are in balance with each other, nothing is wrong. Disruption of this balance could lead to illness in the gut itself or in other places in the body. Determinations of gut microbes in patients with IMID show that they have a different composition of gut microbes. However, it is not clear whether this imbalance between immune system and intestinal microbes is the cause or effect of IMID.
Purpose of the research and research questions:
The hypothesis of our research is the following: disruption of the balance between the immune system and gut microbes play an important role in IMID, both in the gut and elsewhere in the body.
The aim of our research: By mapping the disrupted response of immune cells to gut microbes in IMID patients, we want to be able to better predict how the disease will develop and what medication the patient needs.
This leads to the following sub-questions for both different IMID and the healthy situation:
1. What is the composition of the immune system?
2. Which (inflammatory) substances do the immune cells produce?
3. What are the interactions between the immune system and the gut microbes?
4. How can we get the immune system back in balance with medicines and treatments?
The expectation is that we can better distinguish different forms of IMID if we do not look at the sick organ but at the error in the immune system. This would allow us to treat patients in a much more targeted way based on the defense error found and, by doing that we would prevent unwanted side effects from the medication. We pay particular attention to T cells, this type of immune cell is specifically involved in a part of the IMID indicated below with “TIMID”. The following TIMIDs will be investigated: type 1 diabetes, colon cancer, celiac disease and Inflammatory Bowel Disease (Crohn’s and Ulcerative Colitis), joint diseases Juvenile idiopathic arthritis and Spondylosing Arthritis and graft versus host disease (transplant rejection disease).
The study conducted by the TIMID Consortium is led by Dr. Janneke Samsom (Erasmus MC) and Prof. dr. Dr. Frits Koning (LUMC): “The unique aspect of our research is that we study the erroneous immune response in diseases, regardless of whether the disease affects the intestine, skin or joint. With this we hope to be able to better predict which treatment works for which patient” Samsom says.
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