Kuzmina Zoya, Stroncek David, Pavletic Steven Z
Graft-versus-Host and Autoimmunity Unit, Experimental Transplantation and Immunology Branch, National Cancer Institute NCI, National Institutes of Health, Bethesda, Maryland.
Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
J Clin Apher. 2015 Aug;30(4):224-37. doi: 10.1002/jca.21367. Epub 2014 Dec 26.
Systemic autoimmune diseases (AID) have multiorgan, heterogeneous clinical presentations and are characterized by dysregulation of the immune system, immunodeficiency, irreversible organ damage and increased morbidity and mortality. Preventing or decreasing flares of AID correlate with durable disease control, significant reduction of inflammation and prevention of disability or therapy-related toxicity. There is an urgent need for better treatment of severe, therapy-refractory AID. Extracorporeal photopheresis (ECP) is a cell-based immunomodulatory treatment which has been extensively used in variety of autoimmune disorders for the last two decades. ECP treatment is FDA approved for the treatment of cutaneous T-cell lymphoma (CTCL) with particularly promising results seen in graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HCT). Prolonged therapy is safe, well tolerated and allows reduction of systemic immunosuppression in therapy-refractory patients. Both clinical and experimental evidence suggest that ECP mechanism of action is characterized by apoptosis and phagocytosis of activated cells by antigen-presenting cells (APC), secretion of anti-inflammatory cytokines and stimulation of regulatory T cells (Tregs). The focus of this paper is to review the current evidence of ECP use in the treatment of AID. Here, we summarize the experience of nine major AID from 65 published reports. The key findings demonstrate substantial evidence of ECP feasibility, safety and in some AID also promising efficacy. However, the role of ECP in AID therapy is not established as most published studies are retrospective with limited number of patients and the trials are small or poorly standardized. The available data support future investigations of ECP as a therapeutic modality for the treatment of AID in well-designed prospective clinical studies. J
系统性自身免疫性疾病(AID)具有多器官、异质性的临床表现,其特征为免疫系统失调、免疫缺陷、不可逆的器官损伤以及发病率和死亡率增加。预防或减少AID发作与持久的疾病控制、显著减轻炎症以及预防残疾或治疗相关毒性相关。迫切需要更好地治疗严重的、对治疗耐药的AID。体外光化学疗法(ECP)是一种基于细胞的免疫调节治疗方法,在过去二十年中已广泛应用于多种自身免疫性疾病。ECP治疗已获得美国食品药品监督管理局(FDA)批准用于治疗皮肤T细胞淋巴瘤(CTCL),在异基因造血干细胞移植(HCT)后的移植物抗宿主病(GVHD)中尤其取得了令人鼓舞的结果。长期治疗安全、耐受性良好,并能使治疗耐药患者减少全身免疫抑制。临床和实验证据均表明,ECP的作用机制以抗原呈递细胞(APC)对活化细胞的凋亡和吞噬作用、抗炎细胞因子的分泌以及调节性T细胞(Tregs)的刺激为特征。本文的重点是综述ECP用于治疗AID的当前证据。在此,我们总结了65篇已发表报告中关于九种主要AID的经验。关键发现表明,有大量证据证明ECP具有可行性、安全性,并且在某些AID中也具有有前景的疗效。然而,ECP在AID治疗中的作用尚未确立,因为大多数已发表的研究都是回顾性的,患者数量有限,而且试验规模小或标准化程度差。现有数据支持在精心设计的前瞻性临床研究中对ECP作为AID治疗方法进行进一步研究。J