De Novo Donor-Specific Human Leukocyte Antigen Antibodies in Nonsensitized Kidney Transplant Recipients After T Cell-Mediated Rejection
De Novo Donor-Specific Human Leukocyte Antigen Antibodies in Nonsensitized Kidney Transplant Recipients After T Cell-Mediated Rejection
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DOI：
10.1097/tp.0000000000000448
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发表时间：
2015-05-01
期刊：
影响因子：
6.2
通讯作者：
Anglicheau, Dany
中科院分区：
文献类型：
--
作者：
Chemouny, Jonathan-Maurice;Suberbielle, Caroline;Anglicheau, Dany
背景局部炎症是肾移植中体液免疫反应的潜在原因，并且新生供体特异性抗人白细胞抗原抗体（dnDSA）与急性排斥反应史相关。方法.我们研究了既往未致敏的肾移植受者首次急性T细胞介导的排斥反应（指数TCMR）后dnDSA的频率和后果。结果在2004年9月至2010年12月期间在我们中心接受肾移植的1，054例患者中，我们确定了75例至少有一种TCMR的未致敏患者。在移植后4.4 +/- 6.8个月诊断出指数TCMRs。在指数TCMR后5.1 +/- 3.9个月，使用高灵敏度单抗原人类白细胞抗原珠测定法评估dnDSA，并在16例患者（21%）中检测到dnDSA。发生dnDSA的患者更有可能经历移植前致敏事件，并且在指数TCMR时在临床、生物学和组织学变量上无法区分，尽管小管炎评分倾向于较高（P = 0.079）。这些患者随后发生抗体介导的排斥反应的发生率明显较高（P < 0.001），但在移植后中位随访5.5年后，未观察到死亡删失的移植物存活率降低。随访活检显示抗体介导的变化增加，肾小球炎评分显著升高，C4d染色评分数值升高。结论在细胞排斥反应后监测抗人类白细胞抗原抗体可能是有用的，特别是在移植前暴露于同种异体抗原的患者中，以预测随后的体液事件及其后果。
Background. Local inflammation is a potential cause of humoral alloimmune responses in renal transplantation, and de novo donor-specific anti-human leucocyte antigen antibodies (dnDSAs) have been associated with a history of acute rejection. Methods. We investigated the frequencies and consequences of dnDSAs after a first episode of acute T-cell-mediated rejection (index TCMR) in previously unsensitized kidney transplant recipients. Results. Of the 1,054 patients who underwent kidney transplantation between September 2004 and December 2010 at our center, we identified 75 unsensitized patients with at least one TCMR. Index TCMRs were diagnosed 4.4 +/- 6.8 months after transplantation. The dnDSAs were assessed using the highly sensitive single-antigen human leukocyte antigen bead assay 5.1 +/- 3.9 months after the index TCMR and were detected in 16 patients (21%). Patients who developed dnDSAs were more likely to have experienced pre-transplant sensitizing events and were indistinguishable in their clinical, biologic, and histologic variables at the time of index TCMR, although the tubulitis scores tended to be higher (P = 0.079). These patients experienced a significantly higher incidence of subsequent antibody-mediated rejection episodes (P < 0.001), but reduced death-censored graft survival was not observed after a median follow-up of 5.5 years post-transplantation. Follow-up biopsies revealed increased antibody-mediated changes with significantly higher glomerulitis scores and numerically higher C4d staining scores. Conclusion. Monitoring anti-human leukocyte antigen antibodies after cellular rejection may be useful, especially among patients with a history of pretransplant exposure to alloantigens, to predict subsequent humoral events and their consequences.