The Dumont-UCLA Transplantation Research Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA.
Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Curr Opin Organ Transplant. 2019 Dec;24(6):714-720. doi: 10.1097/MOT.0000000000000705.
Vascularized composite allotransplantation (VCA), a life-enhancing treatment for patients with complex tissue defects, trauma or illness, expounds upon the foundation of solid organ transplantation (SOT), the gold standard in end-stage organ failure. As innate and adaptive immunity remain the fundamental concern, this review highlights divergent immunobiology responses in VCA and SOT recipients.
Host innate immune activation drives peritransplant tissue ischemia-reperfusion injury (IRI). Despite the direct relationship between ischemia-reperfusion (IR)-stress and cell-mediated acute rejection, the mechanism of how IRI may affect VCA loss needs investigation. With skin grafts being highly immunogenic, the incidence of cell-mediated rejection is higher in VCA than SOT; whereas ex-vivo perfusion may exert cytoprotection against IRI in VCA and SOT. New treatment concepts, such as topical immunosuppression or cell-based tolerogenic therapies, may avoid systemic immunosuppression in VCA. Although antibody-mediated rejection is relatively rare in VCA and its disease seems to be distinct from that in SOT, little is known as to whether and how IRI may influence humoral immune rejection cascade in VCA or SOT.
Further understanding of the innate-adaptive immune crosstalk should contribute to much needed development of novel therapies to improve VCA outcomes, based on strategies established in SOT.
血管化复合组织同种异体移植(VCA)为患有复杂组织缺损、创伤或疾病的患者提供了一种提高生活质量的治疗方法,它建立在实体器官移植(SOT)的基础之上,后者是终末期器官衰竭的金标准。由于固有和适应性免疫仍然是关注的核心问题,因此本综述强调了 VCA 和 SOT 受者之间不同的免疫生物学反应。
宿主固有免疫的激活导致移植前组织缺血再灌注损伤(IRI)。尽管缺血再灌注(IR)应激与细胞介导的急性排斥反应之间存在直接关系,但 IRI 如何影响 VCA 丧失的机制仍需研究。由于皮肤移植物具有高度的免疫原性,VCA 中的细胞介导排斥反应发生率高于 SOT;而体外灌注可能对 VCA 和 SOT 中的 IRI 发挥细胞保护作用。新的治疗概念,如局部免疫抑制或基于细胞的耐受治疗,可能避免 VCA 中的全身免疫抑制。尽管抗体介导的排斥反应在 VCA 中相对罕见,其疾病似乎与 SOT 中的不同,但尚不清楚 IRI 是否以及如何影响 VCA 或 SOT 中的体液免疫排斥级联反应。
进一步了解固有-适应性免疫的相互作用,应有助于根据 SOT 中建立的策略,为改善 VCA 结果开发新的治疗方法。