Better recognition and treatment of chronic inflammatory diseases
Recognizing chronic inflammatory diseases before patients develop symptoms? It is still a long way off, but that is the ultimate goal of Femke van Wijk, who was appointed “Professor of Immunology of Tissues" as of 15 October 2020. “And then not only recognize it, but also treat it immediately with the right drug.”
42-year-old Femke is clear about her long-term goal. Since the beginning of her career, she has taken steps in that direction. With her biomedical background, she obtained a PhD for research into peanut allergies in animal models. "Because I became increasingly interested in the human site, I switched to pediatric rheumatology at the WKZ." After an intermediate step of several years of basic research in San Diego, she returned to the UMC Utrecht at the strategic program Infection & Immunity. “I wanted to gain experience in both clinical research and fundamental research. I think that research at the interface of the two could be much better. I want to build that bridge, but then I have to know both sides well.” She now focuses on translational research and works with different teams of clinical researchers. Based on questions from the clinic, she wants to better understand underlying mechanisms in patients and healthy people and then come up with clinical applications.
Immune cells in the tissue
Femke conducts research into chronic inflammatory diseases such as Crohn's disease, rheumatoid arthritis (RA) and atopic dermatitis. Contrary to most immunological research, she not only looks at the T cells in the blood, but especially at those in the tissue. For example, in Crohn's disease, she biopsies bowel samples, In RA, she examines inflammatory fluid from the knee, and in atopic dermatitis she investigates skin biopsies.
“The inflammation is magnified in the local tissue. There you can see exactly which T cells are involved and how they respond to different agents. If you know what happens in tissues, you can see it in the blood as a kind of mirror. By establishing that a certain type of T cell in the affected tissue is active in a patient, the amount of that T cell in the blood is then an indication of the state of the inflammation. If that amount in the blood increases, it may predict the inflammation to flare up. And if you know that, you can initiate a more targeted treatment.”
In this way, Femke's research group found a protein in muscle tissue in children with the serious autoimmune disease juvenile dermatomyositis. “Once we identified it, we discovered that it was also present in the blood in small amounts. Until recently, this condition was monitored by measuring the muscle strength of children, but that is very difficult, especially in small children. Now we can monitor this condition using a blood test. The amount of the relevant biomarker in the blood can also predict the activity of the inflammation.”
Tagged T cells
Femke and her group also look at specific T cells in the blood that are on their way to or come from the relevant inflammation. “Each T cell has its own task, one goes to the skin, the other to the intestine. For that reason, T cells are all tagged. If you can recognize those tags, you can zoom in on those T cells that, for example, go to or come from that inflammation in the gut. That creates opportunities to change the course of the disease."
Research on T cells in tissues is also trying to explain why some people suffer from serious drug side effects much more than others. As soon as that can also be predicted, one can adjust the medication accordingly. Another application is immunotherapy for cancer. “In some patients, this therapy leads to, for example, a bowel inflammation that is so severe that the treatment has to be discontinued. By finding out exactly which T cells cause the inflammation in the intestinal tissue, the therapy may be adapted accordingly.”
Improved technique
The new chair "Immunology of Tissues" is placed in the CTI (Center for Translational Immunology) within the strategic program Infection & Immunity, but also has many interfaces with strategic program Child Health. The fact that this chair did not exist previously is because it has only recently become clear how important T cells are for the tissues. “In addition, our techniques have been greatly improved in recent years, so that we can actually see at a cellular level how T cells behave.”
With her appointment, Femke expects to contribute to the unraveling of the disease-transcending mechanisms of the immune system and their application for patients. “We want to detect chronic inflammatory diseases sooner and treat them in a targeted manner.”