Oostingh Gertie J, Davies Hugh F S, Tang Kerrie C G, Bradley J Andrew, Taylor Craig J
Tissue Typing Laboratory, Addenbrooke's NHS Trust, Cambridge, UK.
Am J Transplant. 2002 Mar;2(3):267-73. doi: 10.1034/j.1600-6143.2002.20312.x.
We have previously shown that IgG HLA specific antibodies in the sera of highly sensitised patients awaiting renal transplantation can cross-react with swine leukocyte antigens (SLA). In this study we determined the frequency of patient serum IgG HLA specific antibody binding to a porcine lymphocyte panel and the likelihood of locating a cross-match negative pig donor for sensitised patients. Serum samples (n = 82) were obtained from 35 sensitised [current IgG panel reactive antibodies (PRA) > 10%] and seven nonsensitised patients awaiting renal transplantation at Addenbrooke's Hospital, Cambridge, UK. Fifty sera had IgG HLA specific PRA of 11-84%, 20 had IgG PRA of >84% and 12 had 0% PRA (negative controls). Sera were absorbed with porcine erythrocytes to remove xenoreactive natural antibodies and tested for cross-reactive IgG HLA specific antibody binding by flow cytometry against a panel of porcine lymphocytes obtained from 23 human decay accelerating factor (hDAF) transgenic pigs. A total of 1,884 cross-match combinations were tested and 369 (20%) gave a positive porcine lymphocyte cross-match. For sera from sensitised patients with IgG PRA (11-64%), only 6 of 805 (0.75%) cross-match tests were positive. In contrast, for sera from patients with high IgG PRA (>64%), 363 of 805 (45%) cross-match tests were positive (p < 0.0001). There was no difference in the frequency of positive cross-matches between patient sera with IgG PRA 65-84% and highly sensitised patient sera with IgG PRA 85-100% [156/345 (45%) vs. 207/460 (45%)]. This study demonstrates that only patient sera with broadly reactive IgG HLA specific PRA (>64%) cross-react with porcine lymphocytes. If future clinical trials of xenotransplantation are undertaken, it may be of value to select a cross-match-negative pig organ donor for such patients.
我们之前已经表明，等待肾移植的高度致敏患者血清中的IgG HLA特异性抗体可与猪白细胞抗原（SLA）发生交叉反应。在本研究中，我们测定了患者血清IgG HLA特异性抗体与猪淋巴细胞板结合的频率，以及为致敏患者找到交叉配型阴性猪供体的可能性。血清样本（n = 82）取自英国剑桥阿登布鲁克医院等待肾移植的35名致敏患者[当前IgG板反应性抗体（PRA）> 10%]和7名非致敏患者。50份血清的IgG HLA特异性PRA为11 - 84%，20份血清的IgG PRA > 84%，12份血清的PRA为0%（阴性对照）。血清用猪红细胞吸收以去除异种反应性天然抗体，并通过流式细胞术检测针对从23头人衰变加速因子（hDAF）转基因猪获得的一组猪淋巴细胞的交叉反应性IgG HLA特异性抗体结合情况。总共测试了1884种交叉配型组合，其中369种（20%）猪淋巴细胞交叉配型呈阳性。对于IgG PRA为11 - 64%的致敏患者血清，805次交叉配型测试中只有6次（0.75%）呈阳性。相比之下，对于IgG PRA > 64%的患者血清，805次交叉配型测试中有363次（45%）呈阳性（p < 0.0001）。IgG PRA为65 - 84%的患者血清与IgG PRA为85 - 100%的高度致敏患者血清之间的阳性交叉配型频率没有差异[156/345（45%）对207/460（45%）]。本研究表明，只有具有广泛反应性的IgG HLA特异性PRA（> 64%）的患者血清才会与猪淋巴细胞发生交叉反应。如果未来进行异种移植的临床试验，为这类患者选择交叉配型阴性的猪器官供体可能会有价值。
