Complement-dependent cytotoxicity crossmatch (CDC-XM) has been considered for many years the standard of practice for determining compatibility in solid organ transplantation (SOT). However, as this method is laborious, time intensive and lacks sensitivity and specificity, it has been replaced in many laboratories worldwide by flow cytometry crossmatch (FCXM) and/or virtual crossmatch (vXM).

With this study we intend to show the relevance of performing CDC-XM in the era of virtual crossmatching. We retrospectively analyzed 1,007 consecutive T and B cell deceased donor (DD) CDC-XMs performed in parallel using non-treated and dithiothreitol (DTT) treated sera between May 2022 and January 2023 in waitlisted patients with no donor specific antibodies (DSA) against HLA-A, B and/or DR antigens. Thirty five of 1,007 (3.5%) T cell crossmatches and 132 of 1,007 (13.1%) B cell crossmatches were positive with non-treated sera. Correlation with the vXM demonstrated no DSA in any of the positive T cell crossmatches. DSA were also absent in 126/132 positive B cell crossmatches, indicating a high rate of false positive CDC-XM. Indeed, only 4/35 T cell and 13/132 B cell CDC-XM remained positive after treatment with DTT, confirming that false positive reactivity with non-treated sera is high. Class I HLA DSA against C locus antigens were present in 17/1,007 T cell crossmatches and none were detected by CDC-XM (sensitivity = 0%). Similarly, only 6/77 B cell crossmatches with DSA targeting HLA-C, DQ and/or DP antigens were CDC-XM positive (sensitivity = 7.8%). Furthermore, only 4/6 positive B cell CDC-XM were confirmed to have complement binding potential using the C1q assay, suggesting additional false positive reactivity in 2/6 of the positive CDC-XM.

Our study demonstrates that CDC-XM exhibits poor sensitivity, high false positive reactivity (especially without DTT treatment) and does not meaningfully contribute to pre-transplant compatibility testing in the context of vXM based allocation. Furthermore, the use of CDC-XM can unnecessarily delay or even prevent safe and appropriate transplant allocation.

补体依赖性细胞毒性交叉配型 (CDC-XM) 多年来一直被认为是确定实体器官移植 (SOT) 相容性的实践标准。然而，由于这种方法费力、耗时且缺乏敏感性和特异性，因此在世界各地的许多实验室中它已被流式细胞术交叉配血 (FCXM) 和/或虚拟交叉配血 (vXM) 所取代。

通过这项研究，我们打算展示在虚拟交叉配血时代执行 CDC-XM 的相关性。我们回顾性分析了 2022 年 5 月至 2023 年 1 月期间，在没有抗 HLA 供体特异性抗体 (DSA) 的候补患者中，使用未经处理和二硫苏糖醇(DTT) 处理的血清并行进行的 1,007 例连续 T 细胞和 B 细胞死亡供体 (DD) CDC-XM。 -A、B和/或DR抗原。1,007 例 T 细胞交叉配型中的 35 例 (3.5%)和 1,007 例 B 细胞交叉配型中的 132 例 (13.1%) 与未处理的血清呈阳性。与 vXM 的相关性表明，在任何阳性 T 细胞交叉配中都没有 DSA。在 126/132 阳性 B 细胞交叉配型中也不存在 DSA，表明 CDC-XM 假阳性率很高。事实上，在用 DTT 处理后，只有 4/35 T 细胞和 13/132 B 细胞 CDC-XM 保持阳性，证实与未处理血清的假阳性反应性很高。针对 C 位点抗原的 I 类 HLA DSA 存在于 17/1,007 T 细胞交叉配型中，并且 CDC-XM 未检测到（灵敏度 = 0%）。同样，只有 6/77 的 B 细胞与针对 HLA-C、DQ 和/或 DP 抗原的 DSA 交叉匹配呈 CDC-XM 阳性（灵敏度 = 7.8%）。此外，使用 C1q 测定仅确认 4/6 的阳性 B 细胞 CDC-XM 具有补体结合潜力，表明 2/6 的阳性 CDC-XM 具有额外的假阳性反应性。

我们的研究表明，CDC-XM 的敏感性较差，假阳性反应性较高（尤其是未经 DTT 治疗），并且在基于 vXM 的分配背景下对移植前兼容性测试没有任何意义。此外，使用 CDC-XM 可能会不必要地延迟甚至阻止安全且适当的移植分配。