![]() Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) characterized by a dysregulation of self-tolerance toward myelin and persistent activation of autoreactive cells ( 1– 3). Additionally, the study of vaccination in HSCT-treated subjects as a means of evaluating immune responses could further distinguish broad immunosuppression from immune resetting. Since all subjects need to be optimally protected from vaccine-preventable diseases (including COVID-19), there is a need to ensure that vaccination in subjects undergoing HSCT is effective and safe. Considering that memory B cells are disease-promoting and stem-like T cells are multipotent progenitors involved in self-regeneration of central and effector memory cells, investigating the reconstitution of B cell compartment and stem and effector subsets of immunological memory following autologous HSCT could elucidate those mechanisms. Although our understanding of the clinical and immunological effects of autologous HSCT has progressed, further work is required to characterize the mechanisms that underlie treatment efficacy. Immunological studies have demonstrated that autologous HSCT induces a renewal of TCR repertoires, resurgence of immune regulatory cells, and depletion of proinflammatory T cell subsets, suggesting a “resetting” of immunological memory. The rationale of the intervention is to eradicate inflammatory autoreactive cells with lympho-ablative regimens and restore immune tolerance. Autologous hematopoietic stem cell transplantation (HSCT) has been used as treatment in patients with a highly active disease, achieving a long-term clinical remission in most. Disease-modifying treatments (DMTs) are available to dampen the inflammatory aggression but are ineffective in many patients. Multiple sclerosis (MS) is a central nervous system (CNS) disorder, which is mediated by an abnormal immune response coordinated by T and B cells resulting in areas of inflammation, demyelination, and axonal loss. 10Unit of Haematology and Bone Marrow Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.9Deutsches Rheuma-Forschungszentrum, ein Leibniz Institut, Berlin, Germany.8Charité – Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Rheumatology and Clinical Immunology, Berlin, Germany.7Department of Oncology and Metabolism, The University of Sheffield, Sheffield, United Kingdom.6Department of Haematology, Sheffield Teaching Hospitals National Health Service (NHS) Foundation Trust, Sheffield, United Kingdom.5Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield, United Kingdom.4Institute for Translational Neuroscience and Sheffield Neuroscience Biomedical Research Centre (BRC), Sheffield, United Kingdom.3South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals National Health Service (NHS) Foundation Trust, Sheffield, United Kingdom.2Department of Neurology, Neurology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. ![]() 1Division of Neurology, Department of Brain Sciences, Imperial College London, London, United Kingdom.de Silva 3,5 Basil Sharrack 3,4 John Andrew Snowden 6,7 Tobias Alexander 8,9 Raffaella Greco 10 Paolo A. Maria Teresa Cencioni 1 Angela Genchi 2 Gavin Brittain 3,4 Thushan I.
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