Laboratory of Applied Precision Omics (APO),National Heart,Lung and Blood Institute (NHLBI),National Institutes of Health,Bethesda,Maryland,USA; Laboratory of Transplantation Genomics, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health, Bethesda, Maryland, USA; Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland, USA; Pulmonary and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland, USA; Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Office of Biostatistics Research, National Heart, Lung and Blood Institute, Bethesda, Maryland, USA.
Am J Transplant. 2023 Apr;23(4):559-564. doi: 10.1016/j.ajt.2022.12.019. Epub 2023 Jan 19.
The development of donor-specific antibodies after lung transplantation is associated with downstream acute cellular rejection, antibody-mediated rejection (AMR), chronic lung allograft dysfunction (CLAD), or death. It is unknown whether preemptive (early) treatment of de novo donor-specific antibodies (dnDSAs), in the absence of clinical signs and symptoms of allograft dysfunction, reduces the risk of subsequent CLAD or death. We performed a multicenter, retrospective cohort study to determine if early treatment of dnDSAs in lung transplant patients reduces the risk of the composite endpoint of CLAD or death. In the cohort of 445 patients, 145 patients developed dnDSAs posttransplant. Thirty patients received early targeted treatment for dnDSAs in the absence of clinical signs and symptoms of AMR. Early treatment of dnDSAs was associated with a decreased risk of CLAD or death (hazard ratio, 0.36; 95% confidence interval, 0.17-0.76; P < .01). Deferring treatment until the development of clinical AMR was associated with an increased risk of CLAD or death (hazard ratio, 3.00; 95% confidence interval, 1.46-6.18; P < .01). This study suggests that early, preemptive treatment of donor-specific antibodies in lung transplant patients may reduce the subsequent risk of CLAD or death.
肺移植后供体特异性抗体的发展与下游急性细胞排斥、抗体介导的排斥(AMR)、慢性肺移植物功能障碍(CLAD)或死亡有关。在没有移植物功能障碍的临床症状和体征的情况下,预先(早期)治疗新出现的供体特异性抗体(dnDSAs)是否降低随后发生 CLAD 或死亡的风险尚不清楚。我们进行了一项多中心回顾性队列研究,以确定肺移植患者 dnDSAs 的早期治疗是否降低 CLAD 或死亡的复合终点风险。在 445 例患者的队列中,145 例患者在移植后出现 dnDSAs。30 例患者在没有 AMR 临床症状和体征的情况下接受 dnDSAs 的早期靶向治疗。dnDSAs 的早期治疗与 CLAD 或死亡的风险降低相关(风险比,0.36;95%置信区间,0.17-0.76;P <.01)。直到出现临床 AMR 才开始治疗与 CLAD 或死亡的风险增加相关(风险比,3.00;95%置信区间,1.46-6.18;P <.01)。这项研究表明,肺移植患者 dnDSAs 的早期、预防性治疗可能降低随后发生 CLAD 或死亡的风险。