Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA.
Transplantation. 2020 Dec;104(12):2547-2556. doi: 10.1097/TP.0000000000003206.
Angiotensin II type-1 receptor (AT1R) antibodies have been associated with rejection and allograft loss in solid organ transplantation and may act synergistically with HLA donor-specific antibodies (DSA). Our aims were to assess the prevalence of AT1R antibodies and determine if they were associated with allograft dysfunction in pediatric liver transplant recipients.
We performed a retrospective, cross-sectional study of HLA DSA and AT1R antibodies in 2 cohorts of pediatric liver transplant recipients: a stable control cohort with normal allograft function (n = 70) who consented to have serum samples collected for research purposes during a routine clinic visit and a cohort with active allograft dysfunction (n = 9) whose serum samples were collected as part of clinical care.
AT1R antibodies >17 U/mL were detected in 29% of stable control patients and 89% of patients with active allograft dysfunction (P = 0.001). In stable control patients, AT1R antibodies were associated with younger age at transplant (P = 0.010), younger age at time of sample collection (P < 0.001), shorter interval since transplant (P = 0.090), and presence of HLA DSA (P = 0.003). AT1R antibodies in stable control patients were not associated with rejection or allograft loss. However, AT1R antibodies combined with HLA DSA in patients with active allograft dysfunction were associated with rejection and allograft loss.
Our results suggest that AT1R antibodies are more common in patients with active allograft dysfunction and may be a risk factor for worse outcomes. Further research is needed to longitudinally assess the clinical impact of HLA DSA and AT1R antibodies.
血管紧张素 II 型 1 型受体 (AT1R) 抗体与实体器官移植中的排斥反应和移植物丢失有关，并且可能与 HLA 供体特异性抗体 (DSA) 协同作用。我们的目的是评估 AT1R 抗体的患病率，并确定其是否与小儿肝移植受者的移植物功能障碍有关。
我们对两组小儿肝移植受者的 HLA DSA 和 AT1R 抗体进行了回顾性、横断面研究：一组为稳定的对照组，其移植物功能正常（n=70），同意在常规就诊期间采集血清样本用于研究目的；另一组为伴有活动性移植物功能障碍的患者（n=9），其血清样本是在临床治疗过程中采集的。
稳定对照组患者中 29%和活动性移植物功能障碍患者中 89%（P=0.001）检测到 AT1R 抗体 >17 U/mL。在稳定对照组患者中，AT1R 抗体与移植时年龄较小（P=0.010）、样本采集时年龄较小（P<0.001）、移植后时间间隔较短（P=0.090）和存在 HLA DSA 相关（P=0.003）。稳定对照组患者的 AT1R 抗体与排斥反应或移植物丢失无关。然而，在活动性移植物功能障碍患者中，AT1R 抗体与 HLA DSA 同时存在与排斥反应和移植物丢失有关。
我们的结果表明，AT1R 抗体在活动性移植物功能障碍患者中更为常见，可能是预后不良的危险因素。需要进一步研究来纵向评估 HLA DSA 和 AT1R 抗体的临床影响。
