Histocompatibility and Immunogenetics Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Transplantation. 2011 Jul 15;92(1):48-53. doi: 10.1097/TP.0b013e31821eab8a.
Immunomodulatory protocols including intravenous immunoglobulin/rituximab (IVIG/R) are employed to decrease anti-human leukocyte antigen (HLA) antibody levels for patients broadly sensitized to HLA and increase chances for transplantation with a compatible deceased donor (DD). The aim of our study was to identify the optimal antibody levels allowing for selection of compatible DDs for these sensitized patients.
From January 2006 to December 2009, 108 patients broadly sensitized to HLA who had reached the top of the DD waitlist were treated with IVIG/R. Antibody levels were monitored monthly by Luminex-based single-antigen bead assay. The antigens identified to produce positive complement-dependent cytotoxicity crossmatches (XMs; >200,000 standard fluorescence intensity [SFI]/10,000 median fluorescence intensity [MFI]) were determined to be unacceptable and entered into the United Network for Organ Sharing database generating the calculated panel reactive antibody (CPRA). The mean CPRA (mCPRA) for this group was more than 80. DDs were selected based on T-cell flow XMs (FXMs) less than 250 MCS and B-cell FXMs less than 300 mean channel shifts (MCS).
Monthly Luminex-based single-antigen assays showed that the IVIG/R therapy decreased antibody levels for a period of 30 to 120 days. Of the 108 patients treated, 80 (74%) were transplanted and 28 (26%) were not (mCPRA 96 ± 11). Forty-two (53%) patients were transplanted with a positive FXM; 28 (35%) patients (mCPRA 84 ± 25) were transplanted with a negative FXM; and 10 patients (12%; mCPRA 90 ± 19) received zero HLA ABDR mismatched grafts.
After therapy, careful selection of acceptable DD involves the antibody profiling strength and XM results. These approaches provide patients broadly sensitized to HLA with an opportunity for compatible DD transplantation.
免疫调节方案包括静脉注射免疫球蛋白/利妥昔单抗(IVIG/R),用于降低广泛致敏于人类白细胞抗原(HLA)的患者的抗 HLA 抗体水平,并增加与相容的已故供体(DD)进行移植的机会。我们研究的目的是确定允许为这些致敏患者选择相容 DD 的最佳抗体水平。
从 2006 年 1 月至 2009 年 12 月,108 名广泛致敏于 HLA 的患者在 DD 候补名单的顶端接受了 IVIG/R 治疗。每月通过基于 Luminex 的单抗原珠测定法监测抗体水平。通过补体依赖性细胞毒性交叉匹配(XM;>200,000 标准荧光强度[SFI]/10,000 中值荧光强度 [MFI])产生阳性反应的抗原被确定为不可接受,并进入联合器官共享网络数据库生成计算的 panel reactive antibody(CPRA)。该组的平均 CPRA(mCPRA)超过 80。根据 T 细胞流式 XM(FXM)<250 MCS 和 B 细胞 FXM<300 平均通道移位(MCS)选择 DD。
每月进行的基于 Luminex 的单抗原检测显示,IVIG/R 治疗可在 30 至 120 天内降低抗体水平。在接受治疗的 108 名患者中,80 名(74%)接受了移植,28 名(26%)未接受移植(mCPRA 96±11)。42 名(53%)患者的 FXM 呈阳性;28 名(35%)患者(mCPRA 84±25)的 FXM 呈阴性;10 名患者(12%;mCPRA 90±19)接受了零 HLA ABDR 错配供体移植。
治疗后,对可接受 DD 的仔细选择涉及抗体分析强度和 XM 结果。这些方法为广泛致敏于 HLA 的患者提供了接受相容 DD 移植的机会。