Interview with Dr. Britt-Sabina Petersen, University of Kiel, Germany
T-cells are the guardians of our immune system. When they show changes, it can lead to severe inflammatory responses in the body. It is believed that the T-cells in persons who are affected by inflammatory bowel disease don’t work properly. Two proteins that can be found on activated T-cells and that interact with each other are now being analyzed.
Dr. Britt-Sabina Petersen researches one of the corresponding genes at the Institute of Clinical Molecular Biology, Medical Faculty at the University of Kiel, Germany. In this conversation with MEDICA.de, she elaborates on her findings on the TIM-3 molecule.
Dr. Petersen, how many people are approximately affected by inflammatory bowel disease, IBD in short?
Britt-Sabina Petersen: There are approximately 320,000 people, who are affected by IBD in Germany. On a global scale, industrialized nations are affected in particular. There are far less affected patients in the developing nations. This is why researchers have long since suspected that the Western lifestyle contributes to the development of IBD.
You have examined the so-called TIM-3 molecule (TIM = transmembrane immunoglobulin and mucin domain) more closely in your research. Why this protein in particular?
Petersen: The idea originated with the task force surrounding Richard Blumberg at Harvard, which conducted the functional studies on the TIM-3 and CEACAM1proteins. Both of these proteins play a role in activating T-cells. The Harvard group was able to demonstrate that these proteins are indeed interacting with one another. Hyperactivation of T-cells plays a part in IBD. The American colleagues came to us to examine the genetic background more closely. We then took a look at the different rare genetic variations of the TIM-3 gene, which could potentially affect the bonds of these two proteins, because they could be of importance regarding the origins of IBD. We were actually able to identify a variation that occurs more frequently in the affected persons than in healthy control subjects.
To what extent can you now use these findings for further research?
Petersen: We are not just going to concentrate on the TIM-3 gene in the near future. Primarily common human genome variations have been researched until now. However, it has been shown that variations that are less common in the population also play a role. This is why we use the latest sequencing techniques to discover more rare variations that could be relevant to IBD.
You are particularly looking for new gene variants in families with an increased rate of IPD. Can you tell us why?
Petersen: We would like to know what patients within a family have in common. We use this approach to be able to limit what gene variants could play a decisive role in this. We are also looking at patients where the disease has occurred very early on, because the earlier the onset, the less likely it is that environmental factors are an influence and the more we assume there is a genetic cause behind all this. In that case, there could be one or a few variants with enormous influence, which in turn provides clues for new genes.
IBD is divided into different forms of the disease such as Crohn’s disease or ulcerative colitis. Are there genetic differences between these types of diseases?
Petersen: There are overlapping genes in both of these diseases. More than 100 of the 163 genes that we were able to identify for IBD so far appear as risk factors in both diseases. However, there are also genes that are only associated with one of these two diseases. Therefore, there is a common genetic basis for these diseases, but there are also distinct differences.
How high is the risk for IBD patients to develop cancer?
Petersen: Compared to healthy people, patients with inflammatory bowel disease experience a significantly higher risk of developing colon cancer later on. This is linked to chronic intestinal inflammation, which increases the risk of cancer.
Is it true that genetic carriers don’t necessarily need to develop the disease?
Petersen: IBD develops from an interaction between genetic and environmental factors. The genetic risk factors that we know so far also frequently occur in healthy people; they simply increase the risk of getting sick.
What primary overriding objective does basic research pursue in the area of IBD?
Petersen: The long-term goal of inflammatory bowel disease genetic research is to facilitate a personalized treatment that is precisely matched to the patient’s existing gene variants. This way, you could predict for instance which drug is the best for the patient, whereas we currently often need to try out many different drugs.
However, so far genetic testing is not standard with IBD. Basic research currently investigates which other genetic variants play a role. To date, more than 163 genetic loco – meaning genomic locations - could be located in genome-wide association studies. Yet these only explain approximately 30 percent of the genetic component. This means we still have a lot of work ahead of us to understand the complex genetics behind inflammatory bowel disease.