Monitoring antidonor alloantibodies as a predictive assay for renal allograft tolerance/long-term observations in nonhuman primates
Monitoring antidonor alloantibodies as a predictive assay for renal allograft tolerance/long-term observations in nonhuman primates
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DOI：
10.1097/01.tp.0000234786.26511.a4
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发表时间：
2006-09-27
期刊：
影响因子：
6.2
通讯作者：
Cosimi, A. Benedict
中科院分区：
文献类型：
--
作者：
Boskovic, Svjetlan;Kawai, Tatsuo;Cosimi, A. Benedict
背景资料。为了确定可靠的方法来预测慢性排斥反应(CR)在免疫抑制停药后的发展，尽管有诱导耐受的条件，我们评估了非人类灵长类肾移植受者的各种免疫学反应。14只食蟹猴接受了小剂量全身照射、胸腺照射、抗胸腺细胞球蛋白和移植周CD154阻断，然后用环孢素A治疗一个月。受体分别接受供体骨髓输注(A组，n=8)、供体细胞输注(B组，n=2)和供体脾细胞输注(C组，n=4)3组主要组织相容性复合体不匹配肾移植。A组所有受者均出现混合嵌合体，其中4人长期存活，无排斥反应。其余四人要么慢性地或急性地排斥他们的肾移植。B组和C组所有受者均未形成嵌合体，并排斥其同种异体移植。在各种体外检测中，用流式细胞术(FCM)检测抗供体同种异体抗体(ADA)与远期预后的相关性最大。A、B和C组中同时出现抗T细胞和B细胞Ig G ADA的5名受者在ADA出现后200天内均出现CR的组织学证据。两名仅出现抗B细胞免疫球蛋白抗体ADA的受者中，其中一人在停用免疫抑制药物两年后和ADA出现1.5年后最终发展为CR。另1例抗B细胞ADA极低的受者未发生慢性肾功能衰竭。在移植肾出现功能或组织学异常之前，用流式细胞术监测ADA对预测移植肾耐受失败是有用的。
Background. In an effort to define reliable assays that might predict postimmunosuppressant-withdrawal development of chronic rejection (CR), despite conditioning for tolerance induction, we evaluated various immunological responses in nonhuman primate renal allograft recipients.Methods. Fourteen Cynomolgus monkeys received low dose total body irradiation, thymic irradiation, antithymocyte globulin, and peritransplant CD 154 blockade, followed by a one-month course of cyclosporine. Recipients underwent major histocompatibility complex mismatched kidney transplantation with donor bone marrow infusion (Group A, n = 8), without donor cell infusion (Group B, n = 2), or with donor splenocyte infusion (Group C, n = 4).Results. All Group A recipients developed mixed chimerism and four of them survived long-term without rejection. The remaining four rejected their kidney allografts either chronically or acutely. All recipients in Groups B and C failed to develop chimerism and rejected their allografts. Among various in vitro assays, detection of anti-donor alloantibody (ADA) by flow cytometry (FCM) was the most relevant to long-term outcome. All five recipients that developed both anti-T cell and B cell IgG ADA in Groups A, B and C, developed histological evidence of CR within 200 days of the appearance of ADA. One of two recipients that developed only anti-B cell IgG ADA eventually developed CR over two years following discontinuation of immunosuppression and 1.5 years after ADA development. Another recipient with very low anti-B cell ADA has never developed CR.Conclusion. ADA monitoring with FCM assay appears to be useful in predicting the failure of tolerance prior to the development of functional or histologic abnormalities of the renal allograft.