Virtual crossmatch by identification of donor-specific anti-human leukocyte antigen antibodies by solid-phase immunoassay: A 30-month analysis in living donor kidney transplantation
Virtual crossmatch by identification of donor-specific anti-human leukocyte antigen antibodies by solid-phase immunoassay: A 30-month analysis in living donor kidney transplantation
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DOI：
10.1016/j.humimm.2010.01.003
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发表时间：
2010-03-01
期刊：
影响因子：
2.7
通讯作者：
Mohanakumar, Thalachallour
中科院分区：
文献类型：
--
作者：
Morris, Gerald P.;Phelan, Donna L.;Mohanakumar, Thalachallour
肾移植供体的选择取决于对免疫排斥危险因素的准确预测。从历史上看，通过预先形成的抗人白细胞抗原（HLA）抗体（Abs）检查供体细胞裂解的细胞毒性交叉配型（CXM）被认为是免疫排斥的最佳预测因子。然而，人们对通过免疫测定来确定受体血清中的抗 HILA 抗体特异性以预测交叉配型结果并帮助选择供体有很大兴趣。目前抗 HLA 抗体的免疫测定法高度敏感，但免疫测定法检测到的抗体与其在 CXM 和后续移植中的功能相关性之间的相关性尚未明确。在这项研究中，我们回顾性地检验了通过 Luminex 单抗原测定对 149 名连续活体肾移植受者检测供体特异性抗 HLA 抗体 (DSA) 的预测价值。我们证明，通过免疫分析检测 DSA 可以准确预测阴性交叉配型和移植物存活率。然而，由于供体 HLA-DQ 和 -DP 等位基因的分型有限或由于非 HLA Abs，这种方法对于预测阳性交叉配型的敏感性有限。 CXM 的假阳性预测与平均荧光强度较低 (MFI < 2000) 的“弱”抗体检测相关。此外，我们发现 DSA 珠子的 MFI 与阳性对照珠子的 MFI 之比是识别不会导致 CXM 阳性反应的弱 DSA 的更好方法。有趣的是，DSA 较弱且 CXM 阴性的患者在 18 个月的随访期内具有相同的移植物存活率，这表明 DSA 较弱可能不会妨碍移植。 (c) 2010 年由 Elsevier Inc. 代表美国组织相容性和免疫遗传学学会出版。
Selection of donors for kidney transplantation depends on accurate prediction of risk factors for immunologic rejection. Historically, cytotoxicity crossmatch (CXM) examining lysis of donor cells by preformed anti-human leukocyte antigen (HLA) antibodies (Abs) has been considered the best predictor of immunologic rejection. However, there is much interest in defining anti-HILA Ab specificity in recipient sera by immunoassay to predict crossmatch results and aid in donor selection. Current immunoassays for anti-HLA Abs are highly sensitive, though correlation between Abs detected by immunoassay and their functional relevance in CXM and subsequent transplantation is not well defined. in this study, we retrospectively examined the predictive value of detection of donor-specific anti-HLA Abs (DSA) by Luminex Single Antigen assay from 149 consecutive living donor kidney transplant recipients. We demonstrate that detection of DSA by immunoassay accurately predicted negative crossmatch and graft survival. However, this approach had limited sensitivity for predicting positive crossmatch, attributable to either limited typing of donor HLA-DQ and -DP alleles or due to non-HLA Abs. False-positive prediction of CXM correlated with detection of "weak" Abs with low mean fluorescence intensity (MFI < 2000). Furthermore, we found that a ratio of the MFI of the DSA bead to the MFI of the positive control bead was a better method for identifying weak DSA that did not result in CXM-positive reactions. Interestingly, patients with weak DSA and negative CXM had equivalent graft survival over an 18 month follow-up period, suggesting that weak DSA may not preclude transplantation. (c) 2010 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics.