Patients with Asian-type DEL can safely be transfused with RhD-positive blood.
Patients with Asian-type DEL can safely be transfused with RhD-positive blood.
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亚洲型 DEL 患者可以安全地输注 RhD 阳性血液
DOI：
10.1182/blood.2022018152
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发表时间：
2023-04-27
期刊：
影响因子：
20.3
通讯作者：
Fu, Yongshui
中科院分区：
文献类型：
--
作者：
Ji, Yanli;Luo, Yalin;Wen, Jizhi;Sun, Yuanfan;Jia, Shuangshuang;Ou, Chunquan;Yang, Wenbing;Chen, Jingwang;Ye, Hanshen;Liu, Xiangfu;Liang, Yongneng;Lu, Zhigang;Feng, Ying;Wu, Xinzhong;Xiao, Muzhou;Mo, Jiankun;Zhou, Zhenhai;Wang, Zhen;Liao, Zhijian;Chen, Junhu;Wei, Ling;Luo, Guangping;Santoso, Sentot;Fichou, Yann;Flegel, Willy Albert;Shao, Chaopeng;Li, Chengyao;Zhang, Rui;Fu, Yongshui
亚洲型DEL患者可以安全地接受D+红细胞输注。在亚洲型DEL成红细胞中鉴定了全长RHD转录物，并表达D表位的完整库，如D+细胞。亚洲型DEL表型的红细胞（RBC）表达很少的RhD蛋白，在常规检测中被分型为血清学RhD阴性（D-）表型。已提出对亚洲型DEL患者进行RhD阳性（D+）RBC输注，但由于缺乏关于其安全性和潜在机制的直接证据，尚未被普遍采用。我们进行了一项单臂多中心临床试验，以记录D+ RBC输注在亚洲型DEL患者中的结局;在中位随访226天后，没有接受者（0/42; 95%置信区间，0-8.40）产生同种抗D。我们进行了一项大型回顾性研究，在全国4045名血清学D-孕妇中检测同种抗D免疫;仅在真正D-的个体中发现同种抗D（2.63%，79/3009），而在亚洲型DEL的个体中未发现同种抗D（0/1032）。我们进一步回顾性检查了127名血清学D-妊娠妇女，她们发生了同种异体抗D抗体，没有发现亚洲型DEL（0/127）。最后，我们分析了来自亚洲型DEL成红细胞的RHD转录本，并在体外检查了各种RHD转录本表达的抗原表位，发现表达RhD抗原的全长RHD转录本（占总数的0.18%）的丰度较低，携带整个表位库，这可以解释对D+ RBC的免疫耐受性。我们的研究结果提供了多条证据，证明亚洲型DEL患者在输血或妊娠后暴露于D+ RBC时不能产生同种抗D抗体。因此，我们建议亚洲型DEL患者（包括孕妇）考虑输注D+ RBC并停止抗D预防治疗。本临床试验在www.clinicaltrials.gov注册为#NCT03727230。在亚洲，血清学阴性的RhD（D-）个体主要是RhDEL表型，这是一种导致异质性蛋白表达的多态性，包括少量不足以在体外凝集红细胞的全长RhD。这些患者传统上接受D型血，强调血液供应。在42名RhDEL患者的D+输血的前瞻性临床试验中，Ji及其同事证明这些患者中没有一人产生抗体。在一项超过4000例血清学D-患者的回顾性研究中，仅在真正的D-个体中发现了同种抗D抗体，而在RhDEL患者中没有发现，这强烈表明这些个体可以输注D+血液。
Patients with Asian-type DEL may safely receive D+ red cell transfusion. Full-length RHD transcripts were identified in Asian-type DEL erythroblasts and express the complete repertoire of D epitopes like D+ cells. Red blood cells (RBCs) of Asian-type DEL phenotype express few RhD proteins and are typed as serologic RhD-negative (D–) phenotype in routine testing. RhD-positive (D+) RBC transfusion for patients with Asian-type DEL has been proposed but has not been generally adopted because of a lack of direct evidence regarding its safety and the underlying mechanism. We performed a single-arm multicenter clinical trial to document the outcome of D+ RBC transfusion in patients with Asian-type DEL; none of the recipients (0/42; 95% confidence interval, 0-8.40) developed alloanti-D after a median follow-up of 226 days. We conducted a large retrospective study to detect alloanti-D immunization in 4045 serologic D– pregnant women throughout China; alloanti-D was found only in individuals with true D– (2.63%, 79/3009), but not in those with Asian-type DEL (0/1032). We further retrospectively examined 127 serologic D– pregnant women who had developed alloanti-D and found none with Asian-type DEL (0/127). Finally, we analyzed RHD transcripts from Asian-type DEL erythroblasts and examined antigen epitopes expressed by various RHD transcripts in vitro, finding a low abundance of full-length RHD transcripts (0.18% of the total) expressing RhD antigens carrying the entire repertoire of epitopes, which could explain the immune tolerance against D+ RBCs. Our results provide multiple lines of evidence that individuals with Asian-type DEL cannot produce alloanti-D when exposed to D+ RBCs after transfusion or pregnancy. Therefore, we recommend considering D+ RBC transfusion and discontinuing anti-D prophylaxis in patients with Asian-type DEL, including pregnant women. This clinical trial is registered at www.clinicaltrials.gov as #NCT03727230. Serologically negative RhD (D–) individuals in Asia are predominantly of the RhDEL phenotype, a polymorphism that leads to heterogeneous protein expression including a small amount of full-length RhD insufficient to agglutinate red cells in vitro. These patients have traditionally received D– blood, stressing the blood supply. In a prospective clinical trial of D+ transfusion in 42 patients with RhDEL, Ji and colleagues demonstrated that none of these patients developed antibodies. In a retrospective study of over 4000 serologically D– patients, alloanti-D was found only in true D– individuals and in no patients with RhDEL, strongly suggesting that these individuals can be transfused with D+ blood.
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