Toward a Sensible Single-antigen Bead Cutoff Based on Kidney Graft Survival.
Toward a Sensible Single-antigen Bead Cutoff Based on Kidney Graft Survival.
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DOI：
10.1097/tp.0000000000002357
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发表时间：
2019-04
期刊：
影响因子：
6.2
通讯作者：
Otten HG
中科院分区：
文献类型：
--
作者：
Wisse BW;Kamburova EG;Joosten I;Allebes WA;van der Meer A;Hilbrands LB;Baas MC;Spierings E;Hack CE;van Reekum FE;van Zuilen AD;Verhaar MC;Bots ML;Drop ACAD;Plaisier L;Seelen MAJ;Stephan Sanders J;Hepkema BG;Lambeck AJA;Bungener LB;Roozendaal C;Tilanus MGJ;Voorter CE;Wieten L;van Duijnhoven EM;Gelens MACJ;Christiaans MHL;van Ittersum FJ;Nurmohamed SA;Lardy NM;Swelsen W;van der Pant KAMI;van der Weerd NC;Ten Berge IJM;Bemelman FJ;Hoitsma AJ;van der Boog PJM;de Fijter JW;Betjes MGH;Heidt S;Roelen DL;Claas FH;Otten HG
文本中提供了补充数字内容。对于特定 HLA 抗体的单抗原珠呈阳性的解释，文献中尚未达成共识。为了为辩论提供信息，我们研究了各种单抗原珠阳性算法之间的关系，以及由此产生的供体特异性 HLA 抗体 (DSA) 阳性对 3237 例已故供体移植肾移植物长期存活的影响。首先，我们表明，当使用信号背景比而不是绝对中值荧光强度 (MFI) 时，可以大大降低测定间变异性。接下来，我们使用各种 MFI 截止值、信号背景比及其组合来确定移植前 DSA。通过比较 DSA 阳性组和 DSA 阴性组之间的移植物存活率，研究了各种截止值的影响。我们没有观察到各种截止水平对 10 年移植物存活的强烈影响。当使用信号背景比时，发现 DSA 阳性移植物的截止水平和 1 年移植物存活之间存在更强的关系，对于以最低 MFI 作为背景的相同 HLA 基因座的珠子最为明显。关于移植前风险分层，我们提出信号背景比为 6（使用具有最低 MFI 的相同 HLA 基因座的珠子作为背景）截止值 15 与 MFI 截止值 500 相结合，导致 8% DSA 阳性移植物的 1 年和 10 年移植物存活率分别降低 8% 和 21%。
Supplemental Digital Content is available in the text. There is no consensus in the literature on the interpretation of single-antigen bead positive for a specific HLA antibody. To inform the debate, we studied the relationship between various single-antigen bead positivity algorithms and the impact of resulting donor-specific HLA antibody (DSA) positivity on long-term kidney graft survival in 3237 deceased-donor transplants. First, we showed that the interassay variability can be greatly reduced when working with signal-to-background ratios instead of absolute median fluorescence intensities (MFIs). Next, we determined pretransplant DSA using various MFI cutoffs, signal-to-background ratios, and combinations thereof. The impact of the various cutoffs was studied by comparing the graft survival between the DSA-positive and DSA-negative groups. We did not observe a strong impact of various cutoff levels on 10-year graft survival. A stronger relationship between the cutoff level and 1-year graft survival for DSA-positive transplants was found when using signal-to-background ratios, most pronounced for the bead of the same HLA locus with lowest MFI taken as background. With respect to pretransplant risk stratification, we propose a signal-to-background ratio-6 (using the bead of the same HLA-locus with lowest MFI as background) cutoff of 15 combined with an MFI cutoff of 500, resulting in 8% and 21% lower 1- and 10-year graft survivals, respectively, for 8% DSA-positive transplants.