Kueht M, Jindra P, Stevenson H L, Galvan T N, Murthy B, Goss J, Anton J, Abbas R, Cusick M F
Department of Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, United States of America.
Department of Surgery, Baylor College of Medicine, One Baylor Plaza, MS:BCM 504, Houston, TX 77030, United States of America.
Mol Genet Metab Rep. 2021 Jan 13;26:100705. doi: 10.1016/j.ymgmr.2020.100705. eCollection 2021 Mar.
During simultaneous liver-kidney transplantation (SLK) in highly sensitized patients, donor specific anti-human leukocyte antigen antibodies (DSA, HLA) can be present prior to transplant leading to positive crossmatch, yet these recipients have relatively low incidences of acute rejection. The mechanisms and timing underlying immunologic changes that occur intra-operatively remain largely unknown. Therefore, we measured the intra- and peri-operative kinetics of anti-HLA antibodies in highly sensitized SLK recipients. In this study, pre- and post-operative blood samples were obtained from sensitized SLK candidates with documented DSA. Intra-operative samples were obtained from a sub-group of SLK recipients. Pretransplant anti-HLA antibody profiles were created and flow cytometry and anti-human globulin complement-dependent cytotoxic crossmatches were performed. Significant reductions in anti-HLA class I and II DSA were seen intra-operatively shortly after reperfusion of the liver allograft. This effect was most pronounced for anti-HLA class I DSA (mean change, -85%, < 0.05); changes to anti-HLA class II DSA were less robust (mean change, -47%, = 0.15). Importantly, non-DSA anti-HLA antibodies remained unchanged throughout the perioperative period, suggesting the mechanism(s) by which the liver lowers DSA levels are specific to the DSA. These data demonstrate the immunologic benefit of performing SLK is lasting and occurs very shortly after liver reperfusion.
在对高敏患者进行肝肾联合移植（SLK）时，供体特异性抗人白细胞抗原抗体（DSA，HLA）在移植前就可能存在，导致交叉配型呈阳性，但这些受者急性排斥反应的发生率相对较低。术中发生的免疫变化的机制和时间仍 largely 未知。因此，我们测量了高敏 SLK 受者术中及围手术期抗 HLA 抗体的动力学变化。在本研究中，从有记录的 DSA 的高敏 SLK 候选者身上获取术前和术后血样。术中样本从 SLK 受者的一个亚组中获取。创建移植前抗 HLA 抗体谱，并进行流式细胞术和抗人球蛋白补体依赖细胞毒性交叉配型。在肝移植再灌注后不久，术中观察到抗 HLA I 类和 II 类 DSA 显著降低。这种效应在抗 HLA I 类 DSA 中最为明显（平均变化，-85%，<0.05）；抗 HLA II 类 DSA 的变化则不那么明显（平均变化，-47%，=0.15）。重要的是，非 DSA 抗 HLA 抗体在围手术期全程保持不变，这表明肝脏降低 DSA 水平的机制是 DSA 特异性的。这些数据表明进行 SLK 的免疫益处是持久的，并且在肝脏再灌注后很快就会出现。
