Karim Christopher, Panigrahi Anil, Pearl Ronald G, Sodha Neel R, Beaver Thomas M, Pelletier J Peter R, Nuttall Gregory A, Reece T Brett, Erickson Anna, Hedrick Teresa, Liu Kathy, Bentow Stanley, Corash Laurence, Mufti Nina, Varrone Jeanne, Benjamin Richard J
Cerus Corporation, Concord, California, USA.
Stanford University, Stanford, California, USA.
Transfusion. 2025 Feb;65(2):344-353. doi: 10.1111/trf.18117. Epub 2024 Dec 25.
The clinical significance of natural and treatment-emergent antibodies specific for amustaline/glutathione pathogen-reduced red blood cells (PRRBCs) is not known.
A Phase 3, randomized clinical trial of PRRBCs (ReCePI) compared PRRBCs with conventional RBCs in cardiac or thoracic-aorta surgery. Subjects transfused during and for 7 days after surgery were screened for PRRBC-specific antibodies at baseline, 28 and 75 days post-surgery. Subjects with treatment-emergent antibodies were assessed for evidence of hemolysis. Cryopreserved subject RBC samples were assayed by flow cytometry for circulating PRRBCs using an acridine-specific (2S197-2M1) monoclonal antibody, and for human IgG-coated RBCs. RBC-surface acridine density was quantitated using a commercial calibrated phycoerythrin (PE)-bead panel.
Five of 159 (3.1%) PRRBC and zero of 162 conventional RBC recipients developed treatment-emergent PRRBC-specific IgG, low titer antibodies detected 26-80 days post-surgery after exposure to 1-3 PRRBC units, without clinical evidence of hemolysis. DAT and eluate were weak (w+) positive and PRRBC-specific in one subject. A monocyte monolayer assay (MMA) was non-reactive in the three subjects with an interpretable result. Flow cytometry demonstrated circulating PRRBCs in all five subjects expressing surface acridine concentrations at the limit of detection (approximately 150-301 PE molecules/RBC) compared with freshly transfused PRRBCs (approximately 7500 PE molecules/RBC). In some samples, loss of surface acridine expression could not be distinguished from clearance of the PRRBCs.
Treatment-emergent PRRBC-specific antibodies with the characteristics of nonclinically significant antibodies were detected in five subjects transfused with PRRBCs. Flow cytometry demonstrated persistent circulating PRRBCs with minimal surface acridine expression. (www.
gov Identifier NCT03459287).
针对氨甲环酸/谷胱甘肽病原体灭活红细胞（PRRBCs）的天然抗体和治疗中出现的抗体的临床意义尚不清楚。
一项PRRBCs的3期随机临床试验（ReCePI）在心脏或胸主动脉手术中比较了PRRBCs与传统红细胞。在手术期间及术后7天接受输血的受试者在基线、术后28天和75天筛查PRRBC特异性抗体。对出现治疗中抗体的受试者评估溶血证据。使用吖啶特异性（2S197-2M1）单克隆抗体通过流式细胞术检测冷冻保存的受试者红细胞样本中的循环PRRBCs以及人IgG包被的红细胞。使用商业校准的藻红蛋白（PE）珠面板对红细胞表面吖啶密度进行定量。
159名接受PRRBCs输血的受试者中有5名（3.1%）出现治疗中PRRBC特异性IgG，在接触1 - 3个PRRBC单位后，术后26 - 80天检测到低滴度抗体，无溶血的临床证据。一名受试者的直接抗人球蛋白试验（DAT）和洗脱液呈弱阳性（w +）且PRRBC特异性。在三名结果可解释的受试者中，单核细胞单层试验（MMA）无反应。流式细胞术显示所有五名受试者中均有循环PRRBCs，其表面吖啶浓度处于检测限（约150 - 301个PE分子/红细胞），而新鲜输血的PRRBCs表面吖啶浓度约为7500个PE分子/红细胞。在一些样本中，表面吖啶表达的丧失与PRRBCs的清除无法区分。
在5名接受PRRBCs输血的受试者中检测到具有非临床显著抗体特征的治疗中PRRBC特异性抗体。流式细胞术显示循环PRRBCs持续存在，表面吖啶表达极少。（www.CLINICALTRIALS.gov标识符NCT03459287）
