Adverse effect of donor-specific anti-human leukocyte antigen (HLA) antibodies directed at HLA-DP/-DQ on engraftment in cord blood transplantation
Adverse effect of donor-specific anti-human leukocyte antigen (HLA) antibodies directed at HLA-DP/-DQ on engraftment in cord blood transplantation
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DOI：
10.1016/j.jcyt.2022.10.005
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发表时间：
2023-03-08
期刊：
影响因子：
4.5
通讯作者：
Kimura, Takafumi
中科院分区：
文献类型：
--
作者：
Jo, Tomoyasu;Arai, Yasuyuki;Kimura, Takafumi
背景目标：尽管移植前受体中的供体特异性抗人类白细胞抗原（HLA）抗体（DSA）与脐带血移植（CBT）中的移植物衰竭相关，但对DSA而非抗HLA-A、-B或-DRB 1对移植结果的影响仍知之甚少。方法：我们回顾性分析了567名单单位CBT接受者，以评估DSA对HLADP和-DQ对CBT结局的影响。结果：在143名（25.2%）具有抗HLA抗体的受者中，9名携带针对HLA-DP或-DQ的DSA。与没有抗HLA抗体的患者相比，抗HLA-DP或-DQ的DSA与移植后100天显著较低的中性粒细胞植入率（55.6%对91.8%，P = 0.032）和略微较低的血小板植入率（46.7%对75.3%，P = 0.128）相关。HLA-DP或-DQ DSA患者的中性粒细胞和血小板植入时间显著长于无抗HLA抗体的患者（中性粒细胞中的中位数为25 vs 21天，P = 0.002;血小板中的中位数为61 vs 46天，P = 0.014）。与没有抗HLA抗体的患者相比，具有抗HLA-DP或-DQ DSA的患者在第100天的细菌感染累积发生率显著更高（88.9%对57.1%，P = 0.024），无再次移植存活率略低（55.6%对76.8%，P = 0.132）。这些发现表明，针对HLA-DP或-DQ的DSA导致不利的植入，这可能增加细菌感染的风险，并降低CBT后不久的生存率。结论：我们的研究结果表明，评估DSA对HLA-DP和DQ受体选择CB单位之前的重要性。(c)2022国际细胞与基因治疗学会爱思唯尔公司出版
Background aims: While donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) in the recipient before transplantation are associated with graft failure in cord-blood transplantation (CBT), effects of DSAs other than against HLA-A, -B or -DRB1 on transplantation outcomes remained poorly understood. Methods: We retrospectively analyzed 567 single-unit CBT recipients to evaluate impact of DSAs against HLADP and -DQ on CBT outcomes. Results: Among 143 recipients (25.2%) who had anti-HLA antibodies, nine harbored DSAs against HLA-DP or -DQ. DSAs against HLA-DP or -DQ were associated with a significantly lower neutrophil engraftment rate (55.6% versus 91.8%, P = 0.032) and with a marginally lower platelet engraftment rate (46.7% versus 75.3%, P = 0.128) at day 100 after transplantation, compared with patients without anti-HLA antibodies. Time to neutrophil and platelet engraftment in patients with DSAs for HLA-DP or -DQ was significantly longer than that in patients without anti-HLA antibodies (median, 25 versus 21 days, P = 0.002 in neutrophil; median 61 versus 46 days, P = 0.014 in platelet). Cumulative incidence of bacterial infection at day 100 was significantly greater (88.9% versus 57.1%, P = 0.024), and re-transplant-free survival was marginally lower (55.6% versus 76.8%, P = 0.132) in patients with DSAs against HLA-DP or -DQ, compared with those without anti-HLA antibodies. These findings suggest that DSAs against HLA-DP or -DQ lead to unfavorable engraftment, which may increase risk of bacterial infection, and reduce survival soon after CBT. Conclusions: Our results suggest the importance of evaluating DSAs against HLA-DP and -DQ in recipients before selecting CB units. (c) 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc.