Division of Transplant Surgery, Northwestern University Feinberg School of Medicine, Comprehensive Transplant Center, Chicago, IL, USA.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Am J Transplant. 2019 Feb;19(2):381-390. doi: 10.1111/ajt.15007. Epub 2018 Aug 23.
Currently, the ability to predict or monitor the efficacy of HLA antibody-removal therapies is deficient. We previously reported that titration studies are a consistent and accurate means of assessing antibody strength. To test whether titration studies can also predict which patients are better candidates for desensitization, we studied 38 patients from 3 centers (29 receiving plasmapheresis/low-dose intravenous immunoglobulin [IVIg]; 9 patients receiving high-dose IVIg). For patients undergoing plasmapheresis/low-dose IVIg, antibody titer reduction correlated with number of treatment cycles for both class I and II antibodies but only up to approximately 4 cycles. Reduction in titer slowed with additional cycles, suggesting a limit to the efficacy of this approach. Furthermore, initial titer (predesensitization) can guide the selection of candidates for successful antibody-removal treatment. In our experience, patients with antibodies at an initial titer >1:512 could not be reduced to the goal of a negative lymphocyte crossmatch, corresponding to a 1:16 titer, despite a significant increase in the number of treatment cycles. Change in mean fluorescence intensity (MFI) value did not correlate with success of treatment if initial MFI values were >10 000, likely due to single antigen bead saturation. Overall, we present a potential prognostic tool to predict candidacy and a monitoring tool to assess efficacy of desensitization treatment.
目前,预测或监测 HLA 抗体清除疗法疗效的能力还存在不足。我们之前曾报道过,滴定研究是评估抗体强度的一种始终如一且准确的方法。为了测试滴定研究是否也可以预测哪些患者更适合脱敏治疗,我们对来自 3 个中心的 38 名患者(29 名接受血浆置换/低剂量静脉免疫球蛋白 [IVIg];9 名接受高剂量 IVIg)进行了研究。对于接受血浆置换/低剂量 IVIg 的患者,I 类和 II 类抗体的抗体滴度降低与治疗周期的数量相关,但最多只能降低约 4 个周期。随着治疗周期的增加,滴度降低速度减缓,这表明该方法的疗效存在限制。此外,初始滴度(脱敏前)可以指导选择成功的抗体清除治疗候选者。根据我们的经验,尽管治疗周期的数量显著增加,但初始滴度 >1:512 的患者无法将抗体滴度降低到阴性淋巴细胞交叉配型的目标,即 1:16 的滴度。平均荧光强度(MFI)值的变化与治疗的成功与否无关,如果初始 MFI 值>10000,则可能是由于单抗原珠饱和所致。总的来说,我们提出了一种潜在的预测候选者的预后工具和一种评估脱敏治疗效果的监测工具。