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. 2021 Mar 22;12:640935. doi: 10.3389/fimmu.2021.640935

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Copyright © 2021 Lutterotti, Hayward-Koennecke, Sospedra and Martin

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Positioning of immune tolerance in disease stages of MS and key challenges for treatment development. Considerations how tolerization appears most meaningful during the different disease stages of MS (represented also graphically at bottom of figure, relapses indicated by open squares). Abbreviations: CIS, clinically isolated syndrome; RIS, radiologically isolated syndrome; RRMS, relapsing-remitting MS; SPMS, secondary-progressive MS. During RIS and CIS, as well as following highly active immunomodulatory therapy tolerization aims at preventing further evolution or re-occurrence of disease. As single agent treatment during RRMS, tolerization aims at replacing currently approved therapies. Its role in SPMS and primary progressive (PP) MS (not shown) is speculative at present.