活体肾移植体液性排斥反应与抗HLA抗体的研究

目的研究活体肾移植术后体液性排斥反应与抗HLA抗体及其特异性的关系。方法87例活体肾移植患者,分别于肾移植术前1天及术后6个月行流式细胞法群体反应抗体检测(Flow PRA screening test)。同时应用独立抗原免疫磁珠分析法(LAB Single antigen analysis)检测抗HLA抗体的特异性。全部患者于术中、术后两周、术后6个月和1年4个时间段进行移植肾穿刺病理检查。结合患者一般情况、病理诊断及抗HLA抗体检测结果,在体液性排斥反应发生率、预后、相关抗体种类及特异性等方面进行回顾性分析。结果87例患者中,群体反应抗体(PRA)术前1天检测结果均为阴性。术后6个月时28例(32.2%,28/87)为阳性。其中,15例(53.6%,15/28)为非供体特异性抗HLA抗体;13例(46.4%,13/28)存在供体特异性抗体。病理结果提示,供体特异性抗体患者中11例(84.6%,11/13)在术后6个月内出现了严重的抗体介导的体液性排斥反应;术后1年时仍然有5例持续存在体液性排斥,移植肾3年内完全丧失功能,恢复到规律透析状态。非供体特异性抗体患者术后无体液性排斥反应发生。术后抗HLA抗体阴性组与阳性组3年移植肾存活率分别为96.6%和75.0%。结论活体肾移植患者抗HLA抗体的出现与术后急性体液性排斥反应的发生明显相关,特别是术后出现供体特异性抗HLA抗体的患者急性体液性排斥反应的发生率更高,预后更差。肾移植术后严密监测抗HLA抗体的出现对于及时调整免疫抑制方案改善移植肾长期存活具有重要意义。

High Incidence of Humoral Rejection in Living Donor Renal Transplant Recipients with Anti-HLA Antibodies

Objective There are few detailed reports up to now about the newly developed anti-HLA antibodies(Ab) after living donor renal transplantation(RTx). We retrospectively investigated the relationship between the development of anti-HLA Ab and the incidence of humoral rejection(HR) in living donor RTx recipients. Methods The subject included 87 patients who received living kidney allografts at kidney center, Tokyo Women's Medical University. PRA assay(Flow PRA screening test) was performed in all the recipients one day before and six months after the RTx. Meanwhile, the donor specificity of Ab was determined by single bead assay(LAB Single antigen analysis). Graft biopsies were performed respectively as well at 0 hour, 2 weeks, 6 months, 1 year after the RTx. We retrospectively studied these recipients with anti-LA Ab to determine the relationship among HR rate, donor specificity and prognosis. Results In 87 recipients, 59 cases(67.8%) showed negative/negative results and 28 cases(32.2%) showed negative/positive results according to the values of pre-post-transplant Flow PRA screening test. As for the 59 recipients without anti-LA Ab, 8 cases(13.6%) developed HR during 6 months posttransplantation, yet no case did so thereafter. Among the 28 cases with anti-LA Ab, 13 cases(46.4%) had donor-specific Ab and 15 cases(53.6%) had non-onor specific Ab as determined by LAB Single antigen analysis. Eleven(39.3%) of the 28 cases with anti-LA Ab showed evidence of antibody mediated humoral rejection in the graft biopsies performed within 6 months and all of them were detected having donor specific Ab. Furthermore, in the graft biopsies performed 1 year after the RTx, 5 of 11(45.5%) cases mentioned above showed persistent evidence of humoral rejection. All these cases lost their grafts in the coming 2 years and returned to regular hemodialysis. Comparably, no HR happened in other 15 recipients with non-onor specific Ab all the way. The 3-year survival rate of renal graft in posttransplant anti-LA Ab negative and positive groups were 96.6% and 75.0% respectively(P<0.01). Conclusion The development of anti-LA antibodies is markedly associated with higher incidence of acute humoral rejection and worse prognosis in living donor RTx recipients, especially in those with donor-specific Ab. Cautious monitoring for the appearance of anti-LA antibodies should be done after transplantation.