The National Institute for Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, UK.
Curr Opin Rheumatol. 2014 Mar;26(2):219-27. doi: 10.1097/BOR.0000000000000029.
To provide an overview of recent advances and future possibilities for therapeutic tolerance.
Allograft survival despite complete immunosuppressant withdrawal has been demonstrated in selected renal-transplant recipients with haematopoietic chimerism. Early clinical trials of mesenchymal stromal cell therapy have shown promising results in several autoimmune diseases. Regulatory T cells show potential benefit in graft versus host disease, although challenges to ex-vivo expansion remain. Targeted modulation of T-cell function in vivo with monoclonal antibodies has shown beneficial effects in phase II/III trials of multiple sclerosis (alemtuzumab) and type I diabetes mellitus (teplizumab, otelixizumab). Emerging data from animal models suggest an important role for the commensal microbiome in the maintenance and disruption of immune tolerance with parallels in human studies.
After years of slow progress, recent research has reduced the translational gap between animal models and clinical therapeutic tolerance. Early detection of autoimmunity, potentially at preclinical stages, offers a window of opportunity for tolerogenic therapy. Reliable biomarkers of tolerance are urgently needed to provide objective measurements of the effectiveness of tolerogenic therapies, and to allow intelligent immunosuppressant withdrawal in patients whose autoimmune disease is stable.
See the Video Supplementary Digital Content 1 (http://links.lww.com/COR/A8).
提供治疗性耐受的最新进展和未来可能性的概述。
在具有造血嵌合体的选定肾移植受者中，尽管完全停用免疫抑制剂，但同种异体移植物仍能存活。间充质基质细胞治疗的早期临床试验在几种自身免疫性疾病中显示出有希望的结果。调节性 T 细胞在移植物抗宿主病中显示出潜在的益处，尽管体外扩增仍然存在挑战。用单克隆抗体在体内靶向调节 T 细胞功能在多发性硬化症（阿仑单抗）和 1 型糖尿病（替普单抗、otelixizumab）的 II/III 期临床试验中显示出有益的效果。来自动物模型的新数据表明，共生微生物组在维持和破坏免疫耐受方面具有重要作用，在人类研究中也存在类似的作用。
经过多年的缓慢进展，最近的研究缩小了动物模型和临床治疗性耐受之间的转化差距。自身免疫的早期检测，可能在临床前阶段，为耐受治疗提供了机会之窗。急需可靠的耐受生物标志物，以提供对耐受治疗有效性的客观测量，并允许自身免疫性疾病稳定的患者智能地停用免疫抑制剂。
视频摘要可在以下网址查看： 请点击链接查看视频摘要http://links.lww.com/COR/A8。
