New so-called immune reconstitution therapies (IRTs) have the potential to induce long-term or even permanent drug-free remission in people with multiple sclerosis (MS). These therapies deplete components of the immune system with the aim of allowing the immune system to renew itself. Haematopoietic stem cell transplantation, the oral formulation cladribine and the monoclonal antibodies alemtuzumab, rituximab and ocrelizumab are frequently categorized as IRTs. However, the evidence that IRTs indeed renew adaptive immune cell repertoires and rebuild a healthy immune system in people with MS is variable. Instead, IRTs might foster the expansion of those cells that survive immunosuppression, and this expansion could be associated with acquisition of new functional phenotypes. Understanding immunological changes induced by IRTs and how they correlate with clinical outcomes will be instrumental in guiding the optimal use of immune reconstitution as a durable therapeutic strategy. This Perspectives article critically discusses the efficacy and potential mechanisms of IRTs in the context of immune system renewal and durable disease remission in MS.
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The authors acknowledge support by the Swiss National Science Foundation (grant 31003A_169664 to J.D.L.), the German Ministry of Education, Science, Research and Technology (BMBF, German Competence Network of MS (KKNMS)) (grant 01GI1603D to T.R. and grant FKZ01FI1603A to H.W.), the Collaborative Research Centre TR-128 ‘Initiating/Effector versus Regulatory Mechanisms in Multiple Sclerosis – Progress towards Tackling the Disease’ (project A09, A10 and Z02 to H.W.), the National Institute of Health Research (project 16/126/26 to P.A.M.), the National Institute of Health Research Biomedical Research Centre funding scheme to Imperial College London (P.A.M.) and the NIH Penn Autoimmunity Centers of Excellence (A.B.O.).
The authors declare no competing interests.
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Lünemann, J.D., Ruck, T., Muraro, P.A. et al. Immune reconstitution therapies: concepts for durable remission in multiple sclerosis. Nat Rev Neurol (2019) doi:10.1038/s41582-019-0268-z