John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, United Kingdom.
Front Immunol. 2018 Apr 4;9:646. doi: 10.3389/fimmu.2018.00646. eCollection 2018.
Patients with treatment refractory Crohn's disease (CD) suffer debilitating symptoms, poor quality of life, and reduced work productivity. Surgery to resect inflamed and fibrotic intestine may mandate creation of a stoma and is often declined by patients. Such patients continue to be exposed to medical therapy that is ineffective, often expensive and still associated with a burden of adverse effects. Over the last two decades, autologous hematopoietic stem cell transplantation (auto-HSCT) has emerged as a promising treatment option for patients with severe autoimmune diseases (ADs). Mechanistic studies have provided proof of concept that auto-HSCT can restore immunological tolerance in chronic autoimmunity the eradication of pathological immune responses and a profound reconfiguration of the immune system. Herein, we review current experience of auto-HSCT for the treatment of CD as well as approaches that have been used to monitor immune reconstitution following auto-HSCT in patients with ADs, including CD. We also detail immune reconstitution studies that have been integrated into the randomized controlled Autologous Stem cell Transplantation In refractory CD-Low Intensity Therapy Evaluation trial, which is designed to test the hypothesis that auto-HSCT using reduced intensity mobilization and conditioning regimens will be a safe and effective means of inducing sustained control in refractory CD compared to standard of care. Immunological profiling will generate insight into the pathogenesis of the disease, restoration of responsiveness to anti-TNF therapy in patients with recurrence of endoscopic disease and immunological events that precede the onset of disease in patients that relapse after auto-HSCT.
患有难治性克罗恩病（CD）的患者会遭受衰弱性症状、生活质量差和工作生产力降低的困扰。切除发炎和纤维化的肠道的手术可能需要创建一个造口，而这通常会被患者拒绝。这些患者仍然会继续接受无效的药物治疗，这种治疗往往昂贵且仍伴有不良反应的负担。在过去的二十年中，自体造血干细胞移植（auto-HSCT）已成为治疗严重自身免疫性疾病（AD）患者的一种有前途的治疗选择。机制研究提供了概念验证，即 auto-HSCT 可以在慢性自身免疫中恢复免疫耐受，消除病理性免疫反应并深刻重塑免疫系统。在此，我们回顾了 auto-HSCT 治疗 CD 的现有经验，以及用于监测 AD 患者（包括 CD）auto-HSCT 后免疫重建的方法。我们还详细介绍了已纳入随机对照的 Autologous Stem cell Transplantation In refractory CD-Low Intensity Therapy Evaluation 试验的免疫重建研究，该试验旨在测试以下假设：与标准治疗相比，使用减强度动员和调理方案的 auto-HSCT 将是诱导难治性 CD 持续缓解的安全有效的方法。免疫分析将深入了解疾病的发病机制、对复发患者的抗 TNF 治疗的反应性恢复以及在复发后接受 auto-HSCT 的患者中疾病发生前的免疫事件。
