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.

中文翻译：

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免疫重建疗法：多发性硬化症持久缓解的概念。

新的所谓免疫重建疗法 (IRT) 有可能在多发性硬化症 (MS) 患者中诱导长期甚至永久无药物缓解。这些疗法会消耗免疫系统的成分，目的是让免疫系统自我更新。造血干细胞移植、口服制剂克拉屈滨和单克隆抗体阿仑单抗、利妥昔单抗和奥瑞珠单抗经常被归类为 IRT。然而，IRT 确实更新了多发性硬化症患者的适应性免疫细胞库并重建了健康的免疫系统的证据是可变的。相反，IRT 可能会促进那些在免疫抑制下存活的细胞的扩增，而这种扩增可能与获得新的功能表型有关。了解 IRT 引起的免疫学变化以及它们与临床结果的相关性将有助于指导优化使用免疫重建作为一种持久的治疗策略。这篇 Perspectives 文章批判性地讨论了 IRT 在 MS 的免疫系统更新和持久疾病缓解方面的功效和潜在机制。