MOLP8细胞系用于消除达雷妥尤单抗对输血前相容性检测造成的干扰*

doi:10.3969/j.issn.1671-2587.2025.05.009

临床输血与检验 ›› 2025, Vol. 27 ›› Issue (5): 643-648.DOI: 10.3969/j.issn.1671-2587.2025.05.009

MOLP8细胞系用于消除达雷妥尤单抗对输血前相容性检测造成的干扰^*

魏华, 赵静雅, 富文达, 凤琼, 穆士杰, 杨龙飞

第四军医大学唐都医院,陕西西安 710038

收稿日期:2025-09-02 修回日期:2025-09-10 出版日期:2025-10-20 发布日期:2025-10-11
通讯作者: 杨龙飞,主要从事输血医学研究,（E-mail）tdyanglf@fmmu.edu.cn。共同通信作者：穆士杰,主要从事输血医学研究,（E-mail）musj1963@fmmu.edu.cn。
作者简介:魏华,主要从事输血医学研究,（E-mail）tangduweihua@163.com。
基金资助:
^*本课题受唐都医院学科助推计划（No.2024JSYX018）资助

Molp8 Cell Line Eliminating the Interference of Daratumumab on the Compatibility Test in Pretransfusion

WEI Hua, ZHAO Jingya, FU Wenda, FENG Qiong, MU Shijie, YANG Longfei

Department of Transfusion Medicine, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi province 710038

Received:2025-09-02 Revised:2025-09-10 Online:2025-10-20 Published:2025-10-11

摘要/Abstract

摘要： 目的 CD38是临床上治疗多发性骨髓瘤的一个有效靶点,由于红细胞膜上CD38的表达,导致其与CD38单抗结合,对用药后患者的输血前相容性检测产生干扰,影响输血安全和时效。因此,本研究拟建立一种解决输血前相容性检测中抗-CD38单抗药物干扰的新方法。方法首先通过数据库及流式细胞术筛选出高表达CD38的MOLP8细胞系,然后建立使用MOLP8细胞吸附去除干扰方法,优化吸附所需细胞量及吸附时间。通过微柱凝胶法进行抗体筛查,验证细胞吸附是否影响其他意外不规则抗体及血型抗体的检出。最后使用4%多聚甲醛固定细胞,探究MOLP8细胞系保存时间对消除干扰效果的影响。结果流式细胞术结果显示MOLP8细胞上高表达CD38。经微柱凝胶法进行抗体筛查检测分析显示,临床标本30 μL与2×10⁶/个MOLP8细胞在37 ℃共孵育5 min能够有效消除干扰,且未对不规则抗体中的抗D,抗K,抗Fy^b,抗Jk^a抗体检测产生影响。MOLP8细胞经4%多聚甲醛保存14 d消除干扰效果依然良好。结论本研究首次将MOLP8细胞用于解决输血前相容性检测中的抗-CD38单抗药物干扰。MOLP8细胞易于大批量制备,也可短期保存作为一种试剂使用,方法简单快捷,具有一定临床应用潜力。

关键词: 多发性骨髓瘤, 输血前相容性检测, CD38单抗, MOLP8细胞

Abstract: Objective CD38 is an effective target for clinical treatment of multiple myeloma. Due to the expression of CD38 on erythrocyte membrane, it combines with CD38 monoclonal antibody, which interferes with the compatibility test in pretransfusion and affects the safety in blood transfusion. Therefore, this study intends to establish a new method to solve the interference of anti-CD38 monoclonal antibody in the compatibility test. Methods Molp8 cell lines with high expression of CD38 were screened by database and flow cytometry, and then the method of removing interference by Molp8 cell adsorption was established to optimize the amount of cells and adsorption time. Antibody screening was performed by gel method to verify whether cell adsorption affected the detection of irregular antibodies and blood group antibodies. Finally, the cells were fixed with 4% paraformaldehyde to explore the effect of Molp8 cell line preservation time on the elimination of interference. Results flow cytometry showed that CD38 was highly expressed on Molp8 cells. The analysis of antibody screening by gel method showed that 30 μL of clinical samples incubated with 2×10⁶ Molp8 cells at 37 ℃ for 5 min could effectively eliminate the interference, and did not affect the detection of anti-D, anti-K, anti Fy^b and anti Jk^a antibodies in irregular antibodies. Molp8 cells were preserved in 4% paraformaldehyde for 14 days, and the interference elimination effect remains well. Conclusion Molp8 cells were used for the first time to solve the interference of anti-CD38 monoclonal antibody in the compatibility test before blood transfusion. Molp8 cells are easy to prepare and can also be stored for a short time as a reagent. The method is simple and fast, and has a certain potential for clinical application.

Key words: Multiple myeloma, Compatibility test pretransfusion, CD38 monoclonal antibody, Molp8 cells

中图分类号:

R457

魏华, 赵静雅, 富文达, 凤琼, 穆士杰, 杨龙飞. MOLP8细胞系用于消除达雷妥尤单抗对输血前相容性检测造成的干扰^*[J]. 临床输血与检验, 2025, 27(5): 643-648.

WEI Hua, ZHAO Jingya, FU Wenda, FENG Qiong, MU Shijie, YANG Longfei. Molp8 Cell Line Eliminating the Interference of Daratumumab on the Compatibility Test in Pretransfusion[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2025, 27(5): 643-648.

参考文献

[1] 裴燕,董林,赵昕亚,等. 去除CD38单克隆抗体干扰多发性骨髓瘤患者输血相容性检测的策略[J]. 临床检验杂志, 2024,42(8):586-588.
[2] 李转丽,石亚军,白海. 达雷妥尤单抗在血液系统疾病治疗中的应用及其耐药机制的研究进展[J]. 现代肿瘤医学, 2023,31(1):192-196.
[3] 于倩茹,周霞,吴弘英,等. 含达雷妥尤单抗方案在复发难治多发性骨髓瘤患者中的疗效与安全性分析[J]. 中华医学杂志,2024,104(7):521-525.
[4] 高帆,李菲. 达雷妥尤单抗在非多发性骨髓瘤疾病中的研究进展和应用[J]. 中国实验血液学杂志,2023, 31(5):1574-1578.
[5] 中国抗癌协会血液肿瘤专业委员会骨髓瘤与浆细胞疾病学组,中国临床肿瘤学会多发性骨髓瘤专家委员会. 高危多发性骨髓瘤诊断与治疗中国专家共识(2024年版)[J]. 中华血液学杂志,2024,45(5):430-435.
[6] 宋婕,陈李影慧,刘爱萍,等. 低浓度二硫苏糖醇去除CD38单抗干扰输血相容性检测的评估[J]. 中国实验血液学杂志,2022,30(4):1198-1202.
[7] 糜坚青,蔡晓红,王少元,等. CD38单克隆抗体对输血相容性检测干扰及其应对方案的专家共识[J]. 中国输血杂志, 2021,34(4):327-334.
[8] 郑妍,王文婷,穆士杰,等. 凝聚胺法去除经CD38单抗治疗多发性骨髓瘤血型血清学干扰的探讨[J]. 中国输血杂志, 2022,35(8):866-868.
[9] 张德峰,孙胜君,于淑红. 去除CD38单抗对输血相容性检测干扰的方法并文献复习[J]. 临床血液学杂志,2024(8):568-570.
[10] 邵林楠,于卫建,周世航. 单克隆抗-CD38抗体对红细胞血型血清学检测的干扰及解决方法现状[J]. 临床输血与检验,2020,22(6):653-659.
[11] 袁燕,邓超干,蔡钦泉,等. 二巯基乙醇解决CD38单克隆抗体对输血前检测的干扰及疗效分析[J]. 国际检验医学杂志,2022,43(8):1021-1024.
[12] 曾含嫣,林志娟,李志峰,等. 达雷妥尤单抗为基础的方案治疗复发难治性多发性骨髓瘤的有效性及安全性:单中心真实世界数据[J]. 中国实验血液学杂志,2024, 32(3):763-767.
[13] 贺玉钦,陈文明. 达雷妥尤单抗在多发性骨髓瘤中的应用[J]. 临床血液学杂志,2023,36(7):461-467.
[14] MAIORANA E,BORTOLATI M,CROITORU S,et al.ELP protocol: an original approach for the mitigation of anti-CD38 interference[J]. Blood Transfus,2025, 23(3):203-211.
[15] BEVEL N,THORPE M,VANNIASINKAM T.Is drug interference still an issue for pretransfusion testing of patients on anti CD38 and other monoclonal antibody therapies?[J]. Vox Sang,2024,119(8):785-791.
[16] 石军伟,高振甫. 多发性骨髓瘤患者达雷妥尤单抗药物不良反应与血药浓度的关系[J]. 医药论坛杂志,2024, 45(9):954-957.
[17] HABICHT C P,RIDDERS M,GRUEGER D,et al.Mitigation of therapeutic anti-CD38 antibody interference with fab fragments: How well does it perform?[J]. Transfusion,2023,63(4):808-816.
[18] TENORIO M,MORENO JIMÉNEZ G,GARCÍA GUTIÉRREZ V,et al. Validation of daraex to resolve daratumumab-induced interferences in pre-transfusion screen tests[J]. Blood,2019,134:4983.
[19] OOSTENDORP M,LAMMERTS VAN BUEREN J J,DOSHI P,et al. When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy[J]. Transfusion,2015,55(6 Pt 2):1555-1562.
[20] BAIG N A,DUKEK B A,FALBO D K,et al.Daratumumab interference in flow cytometric anti-granulocyte antibody testing can be overcome using non-human blocking antibodies[J]. Vox Sang,2021,116(1):116-122.
[21] SELLENG K,GEBICKA P D,THIELE T.F(ab')(2) fragments to overcome daratumumab interference in transfusion tests[J]. N Engl J Med,2018,379(1):90-91.
[22] SCHMIDT A E,KIRKLEY S,PATEL N,et al.An alternative method to dithiothreitol treatment for antibody screening in patients receiving daratumumab[J]. Transfusion,2015, 55(9):2292-2293.
[23] DE VOOGHT K M K,OOSTENDORP M,VAN SOLINGE W W. Dealing with anti-CD38 (daratumumab) interference in blood compatibility testing[J]. Transfusion, 2016,56(3):778-779.
[24] CHAMI B,OKUDA M,MOAYERI M,et al.Anti-CD38 monoclonal antibody interference with blood compatibility testing: Differentiating isatuximab and daratumumab via functional epitope mapping[J]. Transfusion, 2022, 62(11):2334-2348.
[25] 赫喜荣,张凡,王娜,等. 0.01 mol/L DTT处理意外抗体筛查试剂红细胞以消除达雷妥尤单抗干扰及临床适应性研究[J]. 临床输血与检验,2022,24(6):749-753.
[26] 王斐,陈要臻,胡兴斌. 抗CD-38和抗CD-47单抗药物对输血相容性检测的干扰与应对策略研究进展[J]. 临床输血与检验,2023,25(4):559-564.

MOLP8细胞系用于消除达雷妥尤单抗对输血前相容性检测造成的干扰^*

Molp8 Cell Line Eliminating the Interference of Daratumumab on the Compatibility Test in Pretransfusion

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 11

编辑推荐

Metrics

本文评价

关于本刊

作者中心

在线期刊

访问统计

联系我们

[1]	中国输血协会临床输血学专业委员会. 应对抗CD47抗体药物干扰输血相容性检测的中国专家共识^*[J]. 临床输血与检验, 2025, 27(1): 13-20.
[2]	陈婷婷, 赵丽坤, 卓海龙, 骆群. ABO不同血型在不同保存期内CD38的表达[J]. 临床输血与检验, 2023, 25(5): 613-618.
[3]	向倩, 任诗慧, 李晓明. 伊沙佐米治疗多发性骨髓瘤的疗效性与安全性的Meta分析^*[J]. 临床输血与检验, 2023, 25(2): 243-249.
[4]	赫喜荣, 张凡, 王娜, 王璐璐, 刘希曦, 芦宏凯. 0.01 mol/L DTT处理意外抗体筛查试剂红细胞以消除达雷妥尤单抗干扰及临床适应性研究[J]. 临床输血与检验, 2022, 24(6): 749-753.
[5]	蔡梦洁, 梅仁, 戴兰, 沈文红, 傅琤琤, 朱明清. 多发性骨髓瘤循环肿瘤浆细胞的免疫表型特征及其临床意义^*[J]. 临床输血与检验, 2021, 23(4): 478-482.
[6]	楚海亮, 邢名泉, 葛洪峰. VCD方案联合乌苯美司治疗多发性骨髓瘤疗效及患者预后影响因素分析[J]. 临床输血与检验, 2021, 23(2): 216-221.
[7]	李伟超, 程道胜. CD38单抗治疗多发性骨髓瘤的配血策略[J]. 临床输血与检验, 2020, 22(6): 624-626.
[8]	吕晓华. 异常蛋白凝集干扰交叉配血提示确诊1例多发性骨髓瘤[J]. 临床输血与检验, 2020, 22(4): 443-445.
[9]	聂丽容, 李庆华, 梁亮, 何红华, 马境志. 硼替佐米联合化疗对多发性骨髓瘤的治疗效果及对VEGF、IL-6、IL-17的影响[J]. 临床输血与检验, 2020, 22(2): 211-214.
[10]	冶薇, 程虹, 封敏. 血清DKK1、β2-微球蛋白水平与多发性骨髓瘤患病程度的相关性^*[J]. 临床输血与检验, 2019, 21(6): 564-567.
[11]	曹伟, 王冰莹, 曹颖, 杨勇, 贾延伟, 杜鸿. 多发性骨髓瘤M蛋白Ig类型改变的探讨^*[J]. 临床输血与检验, 2019, 21(1): 65-67.