Saris Anno, Kerkhoffs Jean Louis, Norris Philip J, van Ham S Marieke, Ten Brinke Anja, Brand Anneke, van der Meer Pieter F, Zwaginga Jaap Jan
Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands.
Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Transfusion. 2019 Feb;59(2):470-481. doi: 10.1111/trf.15056. Epub 2018 Nov 30.
Platelet transfusions can induce alloimmunization against HLA antigens. The use of pathogen-reduced platelet concentrates (PCs) was suggested to reduce HLA alloimmunization and concomitant transfusion refractoriness.
This study investigated HLA alloimmunization in available samples from 448 hemato-oncological patients who were randomized for the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) trial to receive either untreated or pathogen-reduced PCs (Mirasol, Terumo BCT Inc.). Anti-HLA Class I and II antibodies were determined before the first platelet transfusion and weekly thereafter using multiplex assay with standard cutoffs to detect low- as well as high-level antibodies.
When using the lower cutoff, in patients who were antibody negative at enrollment, 5.4% (n = 12) developed anti-HLA Class I antibodies after receiving untreated PCs, while this was significantly higher in patients receiving pathogen-reduced PCs, 12.8% (n = 29; p = 0.009, intention-to-treat [ITT] analysis). A similar but nonsignificant trend was observed in the per-protocol (PP) analysis (5.4% vs. 10.1%; p = 0.15). HLA class II antibody formation was similar between both types of PCs in the ITT analysis, while the PP analysis showed a trend toward lower immunization after receiving pathogen-reduced PCs. Multivariate analysis identified receiving pathogen-reduced platelets as an independent risk factor for HLA Class I alloimmunization (ITT: odds ratio [95% confidence interval] = 3.02 [1.42-6.51], PP: odds ratio [95% confidence interval] = 2.77 [1.00-5.40]), without affecting HLA Class II alloimmunization. When using the high cutoff value, the difference in HLA Class I alloimmunization between study arms remained significant in the ITT analysis and again was not significant in the PP analysis.
Our data clearly indicate that Mirasol pathogen inactivation does not prevent HLA Class I or II alloimmunization after platelet transfusions.
血小板输注可诱导针对人类白细胞抗原（HLA）的同种免疫。有人建议使用经过病原体灭活的血小板浓缩物（PCs）来减少HLA同种免疫及随之而来的输血难治性。
本研究调查了448例血液肿瘤患者现有样本中的HLA同种免疫情况，这些患者被随机分配至病原体灭活评估与预测分析评分（PREPAReS）试验，以接受未处理的或经过病原体灭活的PCs（Mirasol，Terumo BCT公司）。在首次血小板输注前及之后每周使用多重检测法及标准临界值来检测抗HLA I类和II类抗体，以检测低水平及高水平抗体。
当使用较低临界值时，在入组时抗体阴性的患者中，接受未处理PCs的患者有5.4%（n = 12）在接受输注后产生了抗HLA I类抗体，而接受经过病原体灭活PCs的患者中这一比例显著更高，为12.8%（n = 29；p = 0.009，意向性分析[ITT]）。在符合方案（PP）分析中观察到类似但不显著的趋势（5.4%对10.1%；p = 0.15）。在ITT分析中，两种类型PCs之间HLA II类抗体形成情况相似，而PP分析显示接受经过病原体灭活PCs后免疫反应有降低趋势。多变量分析确定接受经过病原体灭活的血小板是HLA I类同种免疫的独立危险因素（ITT：优势比[95%置信区间]= 3.02[1.42 - 6.51]，PP：优势比[95%置信区间]= 2.77[1.00 - 5.40]），且不影响HLA II类同种免疫。当使用高临界值时，研究组之间HLA I类同种免疫的差异在ITT分析中仍显著，而在PP分析中再次不显著。
我们的数据清楚表明，Mirasol病原体灭活并不能预防血小板输注后HLA I类或II类同种免疫。
