Refractory Celiac Disease: from basic insights to therapy

Celiac disease is a common disease of the small intestine. There is only one effective treatment option: a gluten-free diet. In very rare cases, patients do not respond to a gluten-free diet and develop malignant cells in the small intestine. This is called refractory celiac disease type II (RCDII). RCDII is a severe disease and some RCDII patients pass away due to a lack of effective treatment strategies or due to the development of an even more aggressive form of lymphoma, namely enteropathy-associated T-cell lymphoma (EATL). In this thesis, we describe the current pharmacological approaches under development for the treatment of celiac disease. For RCDII, we describe the efficacy of a new targeted treatment modality: tofacitinib. Moreover, we describe the detailed characterization of the intestinal and peripheral immune system in patients with celiac disease and RCDII. For celiac disease, we explored the potential for plasma B cells acting as antigen-presenting cells in the small intestine. For RCDII, we describe the previously unappreciated heterogeneity of malignant cells in the small intestine. This could explain the variability in disease presentation and response to different treatment strategies. Additionally, we describe immune cells in the tumor microenvironment of RCDII, contributing to knowledge on putative anti- and pro-tumor responses in RCDII<br>