Department of Medicine, Duke University, Durham, North Carolina, USA.
Curr Opin Organ Transplant. 2021 Jun 1;26(3):314-320. doi: 10.1097/MOT.0000000000000878.
Chronic lung allograft dysfunction (CLAD) limits the success of lung transplantation. Among the risk factors associated with CLAD, we recognize pretransplant circulating antibodies against the human leukocyte antigens (HLA), acute cellular rejection (ACR) and antibody-mediated rejection (AMR). This review will summarize current data surrounding management of desensitization, ACR, AMR, and CLAD.
Strategies in managing in highly sensitized patients waiting for lung transplant include avoidance of specific HLA antigens and reduction of circulating anti-HLA antibodies at time of transplant. Several multimodal approaches have been studied in the treatment of AMR with a goal to clear circulating donor-specific antibodies (DSAs) and to halt the production of new antibodies. Different immunosuppressive strategies focus on influence of the host immune system, particularly T-cell responses, in order to prevent ACR and the progression of CLAD.
The lack of significant evidence and consensus limits to draw conclusion regarding the impact of specific immunosuppressive regimens in the management of HLA antibodies, ACR, and CLAD. Development of novel therapeutic agents and use of multicenter randomized clinical trials will allow to better define patient-specific treatments and improve the length and quality of life of lung transplant recipients.
慢性肺移植功能障碍(CLAD)限制了肺移植的成功。在与 CLAD 相关的危险因素中,我们认识到移植前循环中的人类白细胞抗原(HLA)抗体、急性细胞排斥(ACR)和抗体介导的排斥(AMR)。本综述将总结围绕脱敏、ACR、AMR 和 CLAD 管理的现有数据。
在等待肺移植的高度致敏患者中,管理策略包括在移植时避免特定的 HLA 抗原和减少循环中的抗 HLA 抗体。已经研究了几种多模式方法来治疗 AMR,目的是清除循环供体特异性抗体(DSA)并阻止新抗体的产生。不同的免疫抑制策略侧重于影响宿主免疫系统,特别是 T 细胞反应,以防止 ACR 和 CLAD 的进展。
缺乏显著证据和共识限制了对特定免疫抑制方案在 HLA 抗体、ACR 和 CLAD 管理中的影响得出结论。新型治疗药物的开发和多中心随机临床试验的使用将能够更好地确定针对特定患者的治疗方法,并提高肺移植受者的寿命和生活质量。