Red-blood-cell alloimmunisation in relation to antigens' exposure and their immunogenicity: a cohort study

Red-blood-cell alloimmunisation in relation to antigens' exposure and their immunogenicity: a cohort study
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DOI:
10.1016/s2352-3026(16)30019-9
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发表时间:
2016-06-01
期刊:
影响因子:
24.7
通讯作者:
van der Bom, Johanna G.
van der Bom, Johanna G.
中科院分区:
医学1区
文献类型:
--
作者:
Evers, Dorothea;Middelburg, Rutger A.;van der Bom, Johanna G.

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根据受体抗原匹配供体红细胞可防止同种免疫。了解红细胞抗原的免疫原性有助于优化风险适应性匹配策略。我们着手评估的免疫原性的红细胞antigens.Methods在一个事件的新用户队列以前非输血,非allimmunised白色患者接受非扩展匹配的红细胞输血在2006年和2013年之间的6家荷兰医院,我们确定了每例患者的不匹配的红细胞单位的累积数量。我们使用多重插补来解决缺失的抗原数据。使用Kaplan-Meier分析,我们估计每错配抗原剂量作为immunoglobulination.Findings的措施,54347例患者评估,21512累积同种异体免疫发病率包括在我们的研究。所有输血患者中有474例(2.2%)发生同种抗体,在接受40个单位后,累积同种免疫发生率增加至7.7%(95% CI 4.9-11.2)。抗原C、c、E、K和Jk(a)占我们队列中所有同种免疫的78%。K、E和C-w是最具免疫原性的抗原(2个错配单位后的累积免疫发生率为K 2.3% [ 95% CI 1.0-4.8],E 1.5% [0.6-3.0],C-w 1.2% [0.0-10.8])。这些抗原的免疫原性是Fy(a)的8.7倍(对K)、5.4倍(对E)和4.6倍(对C-w)。其次是免疫原性最强的抗原,依次是e(免疫原性是Fy(a)的1.9倍)、Jk(a)(1.9倍)和c(1.6倍)。我们的研究结果强调,供体-受体红细胞匹配策略将是最有效的,主要集中在预防C,C,E,K和JK(a)同种免疫。Fy(a)匹配的临床相关性较低。由种族背景决定的抗原频率的变化阻止将这些结论外推到非白人人群。
Background Matching donor red blood cells based on recipient antigens prevents alloimmunisation. Knowledge about the immunogenicity of red-blood-cell antigens can help optimise risk-adapted matching strategies. We set out to assess the immunogenicity of red-blood-cell antigens.Methods In an incident new-user cohort of previously non-transfused, non-alloimmunised white patients receiving non-extended matched red-blood-cell transfusions in six Dutch hospitals between 2006 and 2013, we determined the cumulative number of mismatched red-blood-cell units per patient. We used multiple imputation to address missing antigen data. Using Kaplan-Meier analysis, we estimated cumulative alloimmunisation incidences per mismatched antigen dose as a measure of immunogenicity.Findings Of 54347 patients assessed, 21512 were included in our study. Alloantibodies occurred in 474 (2.2%) of all transfused patients, with cumulative alloimmunisation incidences increasing up to 7.7% (95% CI 4.9-11.2) after 40 units received. The antigens C, c, E, K, and Jk(a) were responsible for 78% of all alloimmunisations in our cohort. K, E, and C-w were the most immunogenic antigens (cumulative immunisation incidences after 2 mismatched units of 2.3% [ 95% CI 1.0-4.8] for K, 1.5% [0.6-3.0] for E, and 1.2% [0.0-10.8] for C-w). These antigens were 8.7 times (for K), 5.4 times (for E), and 4.6 times (for C-w) as immunogenic as Fy(a). The next most immunogenic antigens were, in order, e (1.9 times as immunogenic as Fy(a)), Jk(a) (1.9 times), and c (1.6 times).Interpretation Red-blood-cell antigens vary in their potency to evoke a humoral immune response. Our findings highlight that donor-recipient red-blood-cell matching strategies will be most efficient when primarily focusing on prevention of C, c, E, K, and Jk(a) alloimmunisation. Matching for Fy(a) is of lower clinical relevance. Variations of antigen frequencies determined by ethnic background prevent extrapolating these conclusions to non-white populations.