De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies.
De novo donor-specific antibodies in belatacept-treated vs cyclosporine-treated kidney-transplant recipients: Post hoc analyses of the randomized phase III BENEFIT and BENEFIT-EXT studies.
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DOI：
10.1111/ajt.14721
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Larsen CP
中科院分区：
文献类型：
--
作者：
Bray RA;Gebel HM;Townsend R;Roberts ME;Polinsky M;Yang L;Meier-Kriesche HU;Larsen CP
供体特异性抗体（dsa）与抗体介导的排斥反应和移植物失败的风险增加有关。在BENEFIT和BENEFIT‐EXT试验中，肾移植受者随机接受基于belatacept强化（MI）、基于belatacept弱效（LI）或基于环孢素的免疫抑制长达7年（84个月）。采用固相流式细胞术筛查，在基线、6个月、12个月、24个月、36个月、48个月、60个月和84个月，以及临床怀疑急性排斥反应发作时，确定HLA特异性抗体的存在/缺失。anti - HLA -阳性患者的样本进一步用单抗原珠试验检测抗体特异性、dsa的存在/不存在以及存在的任何dsa的平均荧光强度（MFI）。在BENEFIT试验中，分别有1.4%、3.5%和12.1%的belatacept MI治疗、belatacept LI治疗和环孢素治疗的患者发生了新的dsa。在BENEFIT‐EXT中相应的值分别为3.8%、1.1%和11.2%。根据Kaplan - Meier分析，在两项研究中，在7年以上的时间里，接受belatacept治疗的患者与接受环孢素治疗的患者的新发DSA发生率显著低于接受环孢素治疗的患者（P < 0.01）。在新发dsa的患者中，基于belatacept的免疫抑制与基于环孢素的免疫抑制相比，MFI数值较低。尽管这些数据是事后得出的，但这些数据表明，基于belatacept的免疫抑制比基于环孢素的免疫抑制更有效地抑制新发DSA的发展。在移植后7年，与接受环孢素治疗的患者相比，接受belatacept治疗的患者表现出较低的新供者特异性HLA抗体发生率。
Donor‐specific antibodies (DSAs) are associated with an increased risk of antibody‐mediated rejection and graft failure. In BENEFIT and BENEFIT‐EXT, kidney‐transplant recipients were randomized to receive belatacept more intense (MI)–based, belatacept less intense (LI)–based, or cyclosporine‐based immunosuppression for up to 7 years (84 months). The presence/absence of HLA‐specific antibodies was determined at baseline, at months 6, 12, 24, 36, 48, 60, and 84, and at the time of clinically suspected episodes of acute rejection, using solid‐phase flow‐cytometry screening. Samples from anti‐HLA‐positive patients were further tested with a single‐antigen bead assay to determine antibody specificities, presence/absence of DSAs, and mean fluorescence intensity (MFI) of any DSAs present. In BENEFIT, de novo DSAs developed in 1.4%, 3.5%, and 12.1% of belatacept MI‐treated, belatacept LI‐treated, and cyclosporine‐treated patients, respectively. The corresponding values in BENEFIT‐EXT were 3.8%, 1.1%, and 11.2%. Per Kaplan‐Meier analysis, de novo DSA incidence was significantly lower in belatacept‐treated vs cyclosporine‐treated patients over 7 years in both studies (P < .01). In patients who developed de novo DSAs, belatacept‐based immunosuppression was associated with numerically lower MFI vs cyclosporine‐based immunosuppression. Although derived post hoc, these data suggest that belatacept‐based immunosuppression suppresses de novo DSA development more effectively than cyclosporine‐based immunosuppression. At 7 years posttransplant, patients treated with belatacept exhibit a lower incidence of de novo donor‐specific HLA antibody compared to recipients treated with cyclosporine.
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