The receptor for advanced glycation endproducts: A potential role in systemic sclerosis

Systemic sclerosis (SSc) is a very heterogeneous disease; every patient with SSc is unique, with variable presentation of clinical features. Furthermore, the disease can show variable activity within one patient. Therefore, correctly characterising the pathophysiological processes that contribute to the early disease course is crucial. In this thesis, we showed that the receptor for advanced glycation endproducts (RAGE) is involved as one of the multiple pathways, and we attempted to make translational steps to clinical application in patients with SSc. RAGE is a cell surface receptor and can bind molecules such as advanced glycation endproducts (AGEs) and high mobility group box 1 (HMGB1), leading to inflammation. The AGE-RAGE axis can be assessed non-invasively using the AGE Reader, as well as measuring the soluble form of RAGE (sRAGE) as a potential serum biomarker for pulmonary arterial hypertension and its outcome. Furthermore, we showed that detecting active calcification in calcinosis cutis is feasible, further characterising specific disease activity in individual patients. The studies presented in this thesis should be considered proofs of concepts that underline the need for further validation of these methods, thereby paving the way for better personalised medicine in patients with SSc.