Immune reconstitution therapy (IRT) is an emerging concept for the treatment of multiple sclerosis (MS) that is given intermittently and can induce long-term remission of MS that is sustained in treatment-free periods. A systematic literature review was performed to identify and summarize current knowledge regarding the short- and long-term immunological consequences of different IRTs and CD20 depleting therapies on the cellular level in patients with MS. A total of 586 articles published between January 2010 and September 2019 were identified and screened; 44 studies met inclusion criteria for the review. All the treatments considered appeared to produce both qualitative and quantitative changes in the immune cell populations of patients with MS that resulted in a more anti-inflammatory immune profile. Autologous hematopoietic stem cell transplantation produced the longest-lasting and greatest effects on a wide range of immune cells. Many patients achieved prolonged depletion of the adaptive immune system when alemtuzumab and cladribine tablets were administered as short courses of therapy; however, a proportion of patients required retreatment to maintain these effects. Alemtuzumab may produce greater depletion of both CD4+ and CD8+ T cells than cladribine tablets, although both treatments similarly deplete B cells. Recovery of B cells before T cell recovery and hyperpopulation of B cells after alemtuzumab may contribute to secondary autoimmunity. Cladribine tablets had a greater effect on B cells than T cells, and no hyperpopulation of B cells was observed after treatment with cladribine tablets. Ocrelizumab and rituximab require regular repeated treatment every 6 months to maintain depletion of B and T cells. Effects of the drug treatments on the innate immune system were minor compared with those on the adaptive immune system. Additional characterization of the cellular changes occurring during IRT and CD20 depletion may lead to further improvement in the understanding of the pathogenesis of MS and the future development of therapies with even longer lasting effects. Although the treatments considered in this review improve quality of life and outcomes for patients with MS, a cure for this debilitating disease is not yet in sight.

中文翻译：

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多发性硬化症中“免疫重建疗法”的免疫学后果：系统评价。

免疫重建疗法（IRT）是间歇性给予的多发性硬化症（MS）治疗的新兴概念，可诱导长期无症状的MS缓解。进行了系统的文献综述，以鉴定和总结有关MS患者不同IRT和CD20耗竭疗法在细胞水平上短期和长期免疫学后果的当前知识。确定并筛选了2010年1月至2019年9月之间发表的586篇文章; 44项研究符合纳入标准。所有被考虑的治疗方法似乎在MS患者的免疫细胞群中产生了质的和量的变化，从而产生了更抗炎的免疫特性。自体造血干细胞移植对多种免疫细胞产生了最长久且最大的作用。当将Alemtuzumab和cladribine片作为短期治疗药物时，许多患者实现了适应性免疫系统的长期耗竭。但是，一部分患者需要重新治疗以维持这些效果。阿仑单抗可能比克拉屈滨片产生更多的CD4 +和CD8 + T细胞耗竭，尽管两种治疗都同样耗竭B细胞。T细胞恢复之前的B细胞恢复和Alemtuzumab之后的B细胞过度繁殖可能有助于继发性自身免疫。克拉屈滨片对T细胞的作用大于T细胞，克拉屈滨片治疗后未观察到B细胞过剩。Ocrelizumab和rituximab每6个月需要定期重复治疗，以维持B细胞和T细胞的消耗。与适应性免疫系统相比，药物治疗对先天免疫系统的影响较小。在IRT和CD20耗竭过程中发生的细胞变化的其他特征可能会导致对MS发病机理的进一步了解以及具有更长持续作用的疗法的未来发展。尽管本综述中考虑的治疗方法可改善MS患者的生活质量和结局，但尚无治愈这种衰弱性疾病的方法。在IRT和CD20耗竭过程中发生的细胞变化的其他特征可能会导致对MS发病机理的进一步了解以及具有更长持续作用的疗法的未来发展。尽管本综述中考虑的治疗方法可以改善MS患者的生活质量和结局，但尚无治愈这种衰弱性疾病的方法。在IRT和CD20耗竭过程中发生的细胞变化的其他特征可能会导致对MS发病机理的进一步了解以及具有更长持续作用的疗法的未来发展。尽管本综述中考虑的治疗方法可改善MS患者的生活质量和结局，但尚无治愈这种衰弱性疾病的方法。