Role of flow cytometry to define unacceptable HLA antigens in lung transplant recipients with HLA-specific antibodies
Role of flow cytometry to define unacceptable HLA antigens in lung transplant recipients with HLA-specific antibodies
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DOI：
10.1097/01.tp.0000204046.89396.c5
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发表时间：
2006-04-15
期刊：
影响因子：
6.2
通讯作者：
Davis, RD
中科院分区：
文献类型：
--
作者：
Appel, JZ;Hartwig, MG;Davis, RD
背景资料。抗供体人类白细胞抗原特异性抗体与肺移植受者的超急性排斥反应和原发移植失败有关。因此，具有人类白细胞抗原特异性抗体的移植候选者通常接受前瞻性交叉配型，以排除具有不可接受的人类白细胞抗原的供者。然而，进行前瞻性交叉配型的需要限制了供者池，并与等待名单时间和死亡率的增加有关。在致敏的肺移植患者中，使用流式细胞术的虚拟交叉配型策略能够准确地确定人类白细胞抗原特异性抗体的特异性，并与预期的交叉配型进行了比较。总共对341例肺移植受者进行了回顾性分析(1992年4月至2003年7月)。16例具有人类白细胞抗原特异性抗体的患者接受了基于流式细胞仪抗体特异性检测的移植，10例患者接受了前瞻性交叉配型。接受虚拟交叉匹配者、接受前瞻性交叉匹配者和无人类白细胞抗原特异性抗体的患者3年后无毛细支气管炎综合征(BOS)的发生率相似(分别为80.4%+/-13.4、85.7%+/-13.2和73.8%+/-2.8，P=0.88)。三年生存率分别为87.5%+/-8.3、70.0%+/-14.5和78.5%+/-2.4，P=0.31。消除致敏患者的预期交叉配型与等待名单上的时间显著减少(P<；0.01)和等待名单死亡率(P<；0.05)相关。所有16名接受虚拟交叉匹配的患者都有阴性的回顾性交叉匹配。通过仔细确定人类白细胞抗原特异性抗体的特异性，流式细胞术方法能够预测阴性交叉配型结果，准确率达到100%，从而能够确定捐赠者的适合性。使用这种虚拟交叉匹配策略，可以在肺移植前安全地省略交叉匹配，从而减少具有人类白细胞抗原特异性抗体的候选人的等待名单时间和死亡率。
Background. Antidonor HLA-specific antibodies have been associated with hyperacute rejection and primary graft failure in lung transplant recipients. Thus, transplant candidates with HLA-specific antibodies generally undergo prospective crossmatching to exclude donors with unacceptable HLA antigens. However, the need to perform a prospective crossmatch limits the donor pool and is associated with increased waiting list times and mortality. A virtual crossmatch strategy using flow cytometry, which enables precise determination of HLA-specific antibody specificity, was compared to prospective crossmatching in sensitized lung transplant candidates.Methods. In all, 341 lung transplant recipients were analyzed retrospectively (April 1992 to July 2003). Sixteen patients with HLA-specific antibodies underwent transplantation based on flow cytometric determination of antibody specificity and 10 underwent prospective crossmatching.Results. Freedom from bronchiolitis obliterans syndrome (BOS) at three years was similar in those undergoing a virtual crossmatch, those undergoing prospective crossmatching, and those without HLA-specific antibodies (80.4%+/- 13.4, 85.7%+/- 13.2, and 73.8%+/- 2.8, respectively, P=0.88). Three-year Survival was also comparable (87.5%+/- 8.3, 70.0%+/- 14.5, and 78.5%+/- 2.4, respectively, P=0.31). Elimination of prospective crossmatching for sensitized patients was associated with a significant decrease in time on the waiting list (P < 0.01) and in waiting list mortality (P < 0.05). All 16 patients undergoing a virtual crossmatch had negative retrospective crossmatches.Conclusions. By carefully determining the specificity of HLA-specific antibodies, flow cytometry methodologies enable the prediction of negative crossmatch results with LIP to 100% accuracy, enabling the determination of appropriateness of donors. Using this virtual crossmatch strategy, crossmatching can be safely omitted prior to lung transplantation, thereby decreasing waiting list time and mortality rates for candidates with HLA-specific antibodies.