STUDY OF THE CLINICAL AND MOLECULAR PHENOTYPE AND NATURAL HISTORY OF ENTEROPATHIES WITH VILLOUS ATROPHY OF UNKNOWN ORIGIN AND THERAPEUTIC POTENTIAL OF BONE MARROW DERIVED MESENCHYMAL STEM CELLS

This PhD project started in 2016 and aimed firstly to define the clinical and molecular phenotype and natural history of enteropathies with villous atrophy of undefined etiology, that need to be clearly distinguished from both coeliac disease, its complications and other non-coeliac enteropathies with villous atrophy due to a known cause. Secondly, we aimed to evaluate the therapeutic potential of mesenchymal stem cell infusions for the treatment of these rare conditions. The main clinical part of this PhD project (February 2018-August 2019) has been carried out in collaboration with the NHS England National Centre for coeliac disease and rare diseases, Sheffield, UK. The results outlined in the thesis show that non-coeliac enteropathies are extremely heterogeneous conditions characterised by different prognoses. More specifically, we have described the largest cohort of patients affected by enteropathies with villous atrophy of unknown origin and we have shown for the first time that they consist of three groups with distinct clinical phenotype and natural history. Mortality in these enteropathies of undefined origin is mainly due to the development of lymphoproliferative complications. Hypoalbuminaemia and age at diagnosis may be useful predictors to identify patients at greatest risk of poor prognosis, therefore needing more aggressive and targeted therapies, such as mesenchymal stem cells.