Identificazione di patterns molecolari in monociti periferici di pazienti affetti da sclerosi multipla con fenotipo primario progressivo.

Multiple Sclerosis is an autoimmune disease that affects the Central Nervous System (CNS) leading to demyelination, axonal and neurological damage, often affecting young adults. MS is considered to be a T cell mediated disease but in recent years different studies have shown that monocytes and monocyte-derived macrophages are also crucial for the development of MS. In this project we aimed to investigate the contribution of the innate immune system in the MS pathology. Peripheral blood monocytes from three groups of individuals: healthy controls, RRMS and PPMS patients have been studied by using a Transcriptomics approach. With this technology, we were able to identify a number of dysregulated pathways specifically induced in monocytes of Primary Progressive Patients (PP) compared to Relapsing Remitting (RR) patients and Healthy controls. We focus our analysis on specific metabolic changes observed in PP-derived monocytes and in a subgroup of RR-monocytes. The most regulated pathway was the Cholesterol Biosynthesis pathway that was strikingly induced in PPMS patients. This pathway has been validated in a different cohort of patients via qPCR-RT and in vitro by using the monocytic cell line ThP1 cell-line.