Immune Tolerance Network, Bethesda, MD, United States.
Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.
Front Immunol. 2018 Feb 2;9:100. doi: 10.3389/fimmu.2018.00100. eCollection 2018.
Autoimmunity represents a broad category of diseases that involve a variety of organ targets and distinct autoantigens. For patients with autoimmune diseases who fail to respond to approved disease-modifying treatments, autologous hematopoietic stem cell transplantation (AHSCT) after high-dose immunosuppressive therapy provides an alternative strategy. Although more than 100 studies have been published on AHSCT efficacy in autoimmunity, the mechanisms that confer long-term disease remission as opposed to continued deterioration or disease reactivation remain to be determined. In a phase II clinical trial, high-dose immunosuppressive therapy combined with autologous CD34 hematopoietic stem cell transplant in treatment-resistant, relapsing-remitting multiple sclerosis (RRMS) resulted in 69.2% of participants achieving long-term remission through 60 months follow-up. Flow cytometry data from the 24 transplanted participants in the high-dose immunosuppression and autologous stem cell transplantation for poor prognosis multiple sclerosis (HALT-MS) trial are presented to illustrate immune reconstitution out to 36 months in patients with aggressive RRMS treated with AHSCT and to highlight experimental challenges inherent in identifying biomarkers for relapse and long-term remission through 60 months follow-up. AHSCT induced changes in numbers of CD4 T cells and in the composition of CD4 and CD8 T cells that persisted through 36 months in participants who maintained disease remission through 60 months. However, changes in T cell phenotypes studied were unable to clearly discriminate durable remission from disease reactivation after AHSCT, possibly due to the small sample size, limited phenotypes evaluated in this real-time assay, and other limitations of the HALT-MS study population. Strategies and future opportunities for identifying biomarkers of clinical outcome to AHSCT in autoimmunity are also discussed.
自身免疫性疾病是一类广泛的疾病，涉及多种器官靶标和不同的自身抗原。对于那些对已批准的疾病修正治疗无反应的自身免疫性疾病患者，在高剂量免疫抑制治疗后进行自体造血干细胞移植（AHSCT）是一种替代策略。尽管已经发表了超过 100 项关于 AHSCT 在自身免疫性疾病中的疗效的研究，但能够长期缓解疾病而不是持续恶化或疾病复发的机制仍有待确定。在一项 II 期临床试验中，高剂量免疫抑制治疗联合难治性、复发缓解型多发性硬化症（RRMS）的自体 CD34 造血干细胞移植，在 60 个月的随访中，69.2%的参与者达到了长期缓解。呈现了来自高剂量免疫抑制和自体干细胞移植治疗预后不良多发性硬化症（HALT-MS）试验的 24 名接受 AHSCT 治疗的侵袭性 RRMS 患者的流式细胞术数据，以说明在 36 个月时患者的免疫重建情况，并强调了通过 60 个月的随访来确定复发和长期缓解的生物标志物所固有的实验挑战。AHSCT 诱导的 CD4 T 细胞数量变化以及 CD4 和 CD8 T 细胞组成的变化在 60 个月的随访中持续存在于那些通过 60 个月的随访维持疾病缓解的参与者中。然而，在通过 AHSCT 从疾病复发中持久缓解的参与者中，研究的 T 细胞表型变化无法清楚地区分，这可能是由于样本量小、实时分析中评估的表型有限以及 HALT-MS 研究人群的其他限制。还讨论了在自身免疫性疾病中识别 AHSCT 临床结果的生物标志物的策略和未来机会。
