PhD defence D. (Denise) van Uden

Below is a brief summary about the dissertation:

Pulmonary hypertension (PH) affects both heart and lungs and is characterized by high blood pressure in the pulmonary arteries and the right ventricle. In recent years, survival of PAH patients has only slightly improved, despite newly developed PAH therapies. The World Health Organization (WHO) classification system divides PH patients in 5 groups based on underlying conditions. Even though these underlying conditions are associated with PH, the underlying pathology is not fully understood yet. Accumulating evidence is pointing to a role for the immune system in the pathogenesis and progression of PAH. To generate new therapeutic treatments it is essential to unravel the immunological mechanisms that underly PH pathology. The research in this thesis focus on a detailed characterization of the immune system in the different PH subgroups. This thesis provides evidence that specific immune phenotypes exist in WHO group 1 PAH subgroups, WHO group 4 CTEPH, and WHO group 5 SAPH. These phenotypes comprise inflammatory mediators in plasma as well as features of T cells, DCs and B cells. To reach this conclusion we have characterized immune cell subsets, their activation and cytokine producing-capacity in detail, resulting in extended data sets. Furthermore, we were able to identify immune profiles which correlated with patient survival. Our studies implicate the Th17 cell subset in PAH and CTEPH disease pathology. Th17 cells are well known to have pathogenic properties and are causally linked to the development of autoimmune diseases. Moreover, peripheral T cells of IPAH and CTEPH patients present with a unique T cell phenotype which is characterized by a reduced cytokine-producing capacity. Further research is required to investigate how the identified immune cells contribute to disease pathology and whether these factors can be used to develop new treatment strategies for PH patients.