Making a general diagnosis more specific

When you feel ill, weak or have strange pains, it’s not always easy to diagnose. Such is the case with many immune-related diseases. Symptoms overlap and vary and there are often no tests that produce a yes-or-no answer. Patients run the risk of falling into a more general category of illness and given a generic treatment plan.

For me, borders can create synergisms between disciplines and it’s fascinating to look at the overlap of diseases. I see the helicopter view of immune-related diseases and get to design tools and develop biomarkers that can differentiate individual patients so that they, too, can receive the best treatment possible.

U-DAIR

At the Utrecht Center for Diagnostic Advances in Immunology Research (U-DAIR), we facilitate cohort research in immune-mediated patients to develop, optimize and validate biomarkers for diagnosis. We also develop methods for harmonizing and standardizing immune monitoring and research. We’re building a biobank of over 30 immunological and inflammatory diseases and complementary databases of patient cohorts.

Our team investigates the inner workings of immune-related diseases – the molecular mechanics, if you will. It’s well-known that the underlying mechanisms of one disease may play a similar role in another, and certain diseases often present the same biological markers. We have particular interest in translating fundamental immunology research into clinical benefit, especially for use in generic diagnostics, in order to better stratify patient populations and provide more specific treatment options.

Changing the norm to help more patients

For example, our research recently changed the dosing advice for a drug already in use for 30 years in stem cell transplantation (Lancet Haemotology, 2017). Before transplantation, the bad cells of the sick immune system in a patient with leukemia are destroyed with chemotherapy. New healthy cells from a donor are then transplanted. Patients are often also given a drug to reduce graft-vs-host disease. Unfortunately, this drug also delays growth of the new immune system. The challenge is thus to give just enough to reduce graft-vs-host disease and enable a fast development of new immune cells to fight virus infections and relapses.

Our research recently changed the dosing advice for a drug already in use for 30 years in stem cell transplantation

Traditionally, the amount of drug given is based on a patient’s bodyweight, and we wondered if there was a better biomarker. We designed a computer model to predict whether the amount of drug affected clinical outcome, and what parameters were a good indication of this. Our findings showed that dosing based on lymphocyte (white blood cell) count rather than only bodyweight, greatly improves chances of survival after a transplant. Our model works well for 90% of patients, and each patient can now receive a customized dose calculation. For patients who don’t fit into the model, we add a biological assay to support the model and can adjust the dose within a day. We’re now in the process of building an immunopharmacology platform, where we can personalize treatment doses and study the pharmacodynamics (how drugs affect the body) for more of these immune modulating compounds.

Do you have an immune-related clinical question?

This is one example of how we can help, and we’re open to all immune-related questions. If you even have a hint that a biomarker may help with a diagnosis, we can help you with your project and validate it, and help implement it into generic diagnostic services. Through our projects, we’ve become acquainted with many different clinical and research fields and consider UDAIR a central hub, where fundamental and clinical research can be conducted, and where we can be creative and innovative together.

Stefan Nierkens, PhD
Head of U-DAIR
PI of Boelens/Nierkens Group
Laboratory of Translational Immunology
UMC Utrecht