In this thesis the role of anti-nuclear antibodies to function as biomarkers in systemic sclerosis has been evaluated. Respectively, the heterogeneity of the disease, the need for biomarkers and... Show moreIn this thesis the role of anti-nuclear antibodies to function as biomarkers in systemic sclerosis has been evaluated. Respectively, the heterogeneity of the disease, the need for biomarkers and the role of auto-antibodies to function as such, with specific attention for anti-topoisomerase I, have been outlined in this thesis. Show less
This thesis focusses on the further unravelling of one of the mechanisms involved in developing Parkinson's disease: the GBA1 gene, encoding the lysosomal enzyme GCase. Several questions are... Show moreThis thesis focusses on the further unravelling of one of the mechanisms involved in developing Parkinson's disease: the GBA1 gene, encoding the lysosomal enzyme GCase. Several questions are addressed: How prevalent are mutations in this gene in the Netherlands and does it affect disease onset (chapter 2 and 5)? What methodological challenges accompany the sequencing of this gene (chapter 3 and 4)? What biomarkers may be used in clinical trials targeting GCase (chapter 6)? And what are the effects of the novel GCase activator LTI-291, when first administered to healthy volunteers (chapter 7) and to GBA-PD patients (chapter 8)? Show less
The studies described in this thesis contribute to the identification of biomarkers for risk stratification in systemic sclerosis (SSc). Luckily, nowadays many SSc prospective cohorts have been set... Show moreThe studies described in this thesis contribute to the identification of biomarkers for risk stratification in systemic sclerosis (SSc). Luckily, nowadays many SSc prospective cohorts have been set up worldwide which allows high-quality research. Given the rarity and the heterogeneity of the disease, relatively large cohorts are needed to draw valuable conclusions. For the studies described in the current thesis, I was able to incorporate data from the Leiden prospective SSc cohort and data from other prospective cohorts in Europe, which made it possible to strengthen the data. In this final chapter, I summarize the main findings of the studies presented in this thesis, put our findings in a broader perspective, discuss future perspectives and formulate research questions that are relevant to assess in the years ahead of us. Show less
