Monitoring immune responsiveness: novel assays to explore immune system dynamics in health and disease

Abstract

Overall, the human immune system is a well-regulated system. However, it may experience disturbances caused by diseases, pathogens, or the use of medications, leading to over- or underactivity. While an overactive immune system can result in the attack of healthy tissue, an underactive immune response increases the risk of the development of infections or cancers. Immunomodulatory drugs can be used to balance such immune system disturbances. However, since these drugs have a significant effect on the immune system, the use of immunomodulatory medication can also result in adverse effects, similar to those seen in immune-related diseases. To prevent immune dysregulation, it is therefore very important to select the right immunomodulatory medication at the right dose. As the immune system comprises many different cells and molecules, this can be a challenge. Monitoring of immune functionality, referred to as immunomonitoring, can be a useful approach to monitor the effects of immunomodulatory drugs on their proximal targets.

In this thesis different methods and applications of immunomonitoring are described. Section 1 depicts the search for biomarkers to monitor the immune function under treatment for transplant patients. In section 2, comparable methods of immunomonitoring were used to gain a better insight in the mechanism of action and the dose-effect relationship of the immunosuppressant HCQ.