Beyond multiple sclerosis susceptibility: disentangling heterogeneity of disease.

Multiple sclerosis (MS) is one of the most common neurological disorders in young adults, affecting around 10,000 people in Belgium and 2.5 million worldwide. The disease can lead to important physical as well as cognitive disability at a time that is crucial in the personal and professional development of patients. MS is characterized by three hallmarks: inflammation, demyelination or destruction of the protective myelin sheath surrounding the neurons, and neuronal loss. The aetiology is unknown but the past few years have seen exciting progress in the field. In the current project, we build on and move beyond our work that unraveled genetic susceptibility and address the sources of patient-to-patient heterogeneity in disease mechanisms. We apply a multi-disciplinary approach, combining different types of data (clinical, genetic, immunological, imaging) in the same study population to capture aspects of heterogeneity related to inflammation, with a focus on B cells, and to demyelination. Understanding disease heterogeneity is crucial in order to address important health challenges, specifically the key challenge of personalized medicine and the development of novel therapeutic strategies addressing more specific or other pathways that are warranted.