Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Best Pract Res Clin Rheumatol. 2010 Aug;24(4):497-511. doi: 10.1016/j.berh.2010.01.007.
Therapeutic tolerance embraces the concept of 'switching off' immunopathology by specifically targeting elements of the immune system. It has been achievable in preclinical models of transplantation and auto-immunity for more than two decades; however, previous attempts to translate to the clinic have been unsuccessful. Nonetheless, an improved understanding of tolerance mechanisms, along with novel therapeutic agents and strategies, are starting to bear fruit in a number of disease areas. True tolerance is achievable in transplantation settings, and long-term remissions can be induced in various auto-immune and atopic conditions. Equivalent outcomes should be achievable in inflammatory arthritis, although this may require an improved understanding of the immune dysregulation that is intrinsic to rheumatoid arthritis (RA), and better definitions of RA autoantigens. Biomarkers of tolerance induction would rapidly advance the field in all therapeutic areas. This article summarises the advances made in other therapeutic areas, and the lessons learned that we can now apply to RA.
治疗性耐受包含“关闭”免疫病理学的概念，即通过专门针对免疫系统的元素。二十多年来，它在移植和自身免疫的临床前模型中已经成为可能；然而，以前将其转化为临床应用的尝试都没有成功。尽管如此，对耐受机制的深入了解，以及新型治疗药物和策略，正在许多疾病领域开始取得成果。在移植环境中可以实现真正的耐受，并且可以在各种自身免疫和特应性疾病中诱导长期缓解。在炎症性关节炎中也应该可以实现等效的结果，尽管这可能需要对类风湿关节炎（RA）固有的免疫失调有更深入的了解，并对 RA 自身抗原有更好的定义。耐受诱导的生物标志物将在所有治疗领域迅速推动该领域的发展。本文总结了在其他治疗领域取得的进展，以及我们现在可以应用于 RA 的经验教训。
