Mechanisms for relapse of disease after autologous hematopoietic stem cell transplantation for multiple sclerosis

Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic intervention for the neurological disease multiple sclerosis (MS).

It is considered standard of care for patients with active MS in many European countries and an estimated 5000 patients have undergone AHSCT for MS world-wide.

Treatment with AHSCT leads to improvement in disability and sustained disease remission in a majority of patients, but about 20% will eventually relapse.

It is currently unknown why some respond with life-long remission and others relapse within a few years.In the last ten years, we have systematically collected blood and cerebrospinal fluid samples from patients undergoing AHSCT and we are now well poised to perform mechanistic studies of the immune system to understand why some patients get an early relapse.

Specifically, we are addressing the questions if relapses after AHSCT are associated with persistent alterations in the local environment within the brain, a failure to eliminate proinflammatory antigen-specific lymphocytes and/or failure to induce a tolerant state of the immune system.To reach our goal, we are performing a comprehensive investigation of the immune system using state of the art technology, such as proximity extension assays and mass cytometry, but also sensitive immunoassays measuring antigen-specific responses in T and B cells developed in-house.

If successful, we will be able to modify current treatment protocols to improve on both safety and efficacy.