Hivelin Mikaël, Siemionow Maria, Grimbert Philippe, Lantieri Laurent
Plastic Surgery Department, Henri Mondor Hospital, University Paris 12, Creteil, France.
Transpl Immunol. 2009 Jul;21(3):117-28. doi: 10.1016/j.trim.2009.04.005. Epub 2009 May 3.
Composite tissue allotransplantations (CTA), were introduced with the first successful hand transplantation and are now a part of reconstructive surgery armamentarium. These reconstructive procedures for non life-threatening indications remain rare due to adverse effects of the associated lifelong immunosuppressive therapy. Indeed, despite recent progress, immunosuppressive therapies remain non-specific to the type of donor and still bear significant risks of serious side effects. Extracorporeal photopheresis (ECP), also called photochemotherapy, has been introduced in the composite tissue allotransplantation field as a part of acute rejection treatment in face transplantations. ECP has been performed after solid organ transplantations as a supportive therapy for acute rejection episodes. It has also been used to treat graft versus host diseases, which can occur after bone marrow or stem cell transplantations. ECP is also used to treat dermatologic diseases, such as cutaneous T-cell lymphoma, or autoimmune diseases, such as scleroderma or pemphigus vulgaris. The principle of ECP is to induce leucocyte apoptosis with UVA radiation after their presentation by psoralens. These leucocytes are immediately re-infused into the patient, where they undergo early apoptosis. Following apoptosis, the leucocytes are engulfed by macrophage or other antigen-presenting cells, such as immature dendritic cells, in an anti-inflammatory cytokine environment. The anti-inflammatory cytokine secretion pattern, with a switch from TH1 to TH2 for CD4+ lymphocytes, and the engulfment by immature cells without co-stimulatory molecules induces anergy, by deleting effector T-cells that responded to the presented antigens. An increase in regulatory T-cells (T-regs) is also induced after ECP and may contribute to allograft acceptance by the recipient. ECP has already been used for the great majority of solid organ transplantations to cure acute rejection episodes or in an attempt to prevent or cure chronic rejections, such as bronchitis obliterans, which occurs after lung transplantation. Considering composite tissue allotransplantations, ECP was used in two face transplantations after the occurrence of second rejection episodes triggered by viral infections. ECP therapy, associated with maintenance immunosuppressive therapy and doses of methylprednisolone, and the control of viral infection, succeeded to reverse the rejection process without the development of other side effects. Despite the fact that the mechanism of action of ECP has not been fully elucidated, this therapy could be a useful supportive therapy during the treatment of acute rejection episodes in composite tissue allotransplantations. In this review, we introduce the interest of ECP implementation in CTA in face allotransplantations.
复合组织同种异体移植（CTA）随着首例成功的手部移植而被引入，如今已成为重建外科手术器械库的一部分。由于相关终身免疫抑制治疗的不良反应，这些用于非危及生命适应症的重建手术仍然很少见。事实上，尽管最近取得了进展，但免疫抑制疗法对供体类型仍无特异性，且仍存在严重副作用的重大风险。体外光化学疗法（ECP），也称为光化学疗法，已作为面部移植急性排斥反应治疗的一部分被引入复合组织同种异体移植领域。ECP已在实体器官移植后作为急性排斥反应发作的支持性疗法进行。它也被用于治疗移植物抗宿主病，这种病可发生在骨髓或干细胞移植后。ECP还用于治疗皮肤病，如皮肤T细胞淋巴瘤，或自身免疫性疾病，如硬皮病或寻常型天疱疮。ECP的原理是在补骨脂素使白细胞呈现后，用紫外线A辐射诱导白细胞凋亡。这些白细胞立即重新注入患者体内，在那里它们经历早期凋亡。凋亡后，白细胞在抗炎细胞因子环境中被巨噬细胞或其他抗原呈递细胞，如未成熟树突状细胞吞噬。抗炎细胞因子分泌模式，即CD4+淋巴细胞从TH1向TH2转变，以及被没有共刺激分子的未成熟细胞吞噬，通过删除对所呈递抗原作出反应的效应T细胞诱导无反应性。ECP后还诱导调节性T细胞（T-regs）增加，这可能有助于受体接受同种异体移植物。ECP已被用于绝大多数实体器官移植，以治愈急性排斥反应发作或试图预防或治愈慢性排斥反应，如肺移植后发生的闭塞性细支气管炎。考虑到复合组织同种异体移植，ECP在两次因病毒感染引发的第二次排斥反应发作后用于面部移植。ECP疗法与维持免疫抑制治疗和甲基泼尼松龙剂量以及病毒感染控制相结合，成功逆转了排斥反应过程，且未出现其他副作用。尽管ECP的作用机制尚未完全阐明，但这种疗法可能是复合组织同种异体移植急性排斥反应发作治疗期间有用的支持性疗法。在本综述中，我们介绍了在面部同种异体移植的复合组织同种异体移植中实施ECP的意义。
