Sumitran-Karuppan S
Division of Clinical Immunology, Karolinska Institute, Huddinge Hospital, Sweden.
Transplantation. 1999 Aug 27;68(4):502-9. doi: 10.1097/00007890-199908270-00010.
We found earlier that there is a close clinical correlation between the presence of histocompatibility leukocyte antigens (HLA) class I-specific donor-reactive antibodies in cross-match serum and a significantly higher frequency of early acute rejection episodes and graft loss during the first year after the transplant.
Specificity determinations of donor-reactive antibodies present in the cross-match serum before allogeneic kidney transplants were performed. In the present study, we compared the suitability and efficiency of (a) platelet absorptions, (b) blocking with anti-HLA monoclonal antibodies in the microcytotoxicity assay, and (c) donor-specific HLA antigen-coated magnetic microbeads in flow cytometric assays for the definition of clinically relevant HLA antibodies and their correlation with early acute rejections and early graft loss.
We found that the microlymphocytoxicity test using donor splenic B lymphocytes often gave positive reactions in the absence of class I or class II antibodies; in other words, a high frequency of false positive reactions was observed. Flow cytometric tests are more sensitive than microlymphocytotoxicity, not only because they are more sensitive, but also because noncomplement-binding antibodies are detected. Platelet absorptions, which detect only reactivity against HLA class I antigens, is insufficient for use in specificity determinations of donor-reactive antibodies. We found that a positive test for HLA antibodies using paramagnetic beads coated with solubilized donor-derived HLA antigens (class I or class II) correlates with early immunological complications after a transplant (P<0.001).
Assays to determine the specificity of donor-reactive antibodies are now available for use during an acute transplant situation. The introduction of such methods is expected to enhance graft survival and to reduce significantly the frequencies of acute rejections episodes after a transplant.
我们先前发现，交叉配血血清中存在组织相容性白细胞抗原（HLA）I类特异性供体反应性抗体与移植后第一年早期急性排斥反应发作频率显著更高以及移植物丢失密切相关。
对同种异体肾移植前交叉配血血清中存在的供体反应性抗体进行特异性测定。在本研究中，我们比较了以下方法在定义临床相关HLA抗体及其与早期急性排斥反应和早期移植物丢失相关性方面的适用性和效率：（a）血小板吸附法，（b）在微量细胞毒性试验中用抗HLA单克隆抗体阻断法，以及（c）供体特异性HLA抗原包被的磁性微珠在流式细胞术检测中的应用。
我们发现，使用供体脾脏B淋巴细胞的微量淋巴细胞毒性试验在不存在I类或II类抗体时常常出现阳性反应；换句话说，观察到高频率的假阳性反应。流式细胞术检测比微量淋巴细胞毒性检测更敏感，这不仅是因为其更灵敏，还因为能检测到非补体结合抗体。仅检测针对HLA I类抗原反应性的血小板吸附法不足以用于供体反应性抗体的特异性测定。我们发现，使用溶解的供体来源HLA抗原（I类或II类）包被的顺磁性微珠检测HLA抗体呈阳性与移植后的早期免疫并发症相关（P<0.001）。
现在有可用于急性移植情况的供体反应性抗体特异性测定方法。预计引入此类方法可提高移植物存活率，并显著降低移植后急性排斥反应发作的频率。
