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免疫吸附降低肾移植候选者供体特异性同种异体抗体的疗效。

Efficacy of immunoadsorption to reduce donor-specific alloantibodies in kidney-transplant candidates.

作者信息

Rostaing Lionel, Congy Nicolas, Aarnink Alice, Maggioni Sébastien, Allal Asma, Sallusto Federico, Game Xavier, Kamar Nassim

机构信息

From the Department of Nephrology and Organ Transplantation, Toulouse, France; Laboratory of Histocompatibility, University Hospital; Toulouse, France; and the Université Paul Sabatier, Toulouse, France.

出版信息

Exp Clin Transplant. 2015 Apr;13 Suppl 1:201-6.

PMID:25894155
Abstract

OBJECTIVES

We implemented a desensitization program at our center to enable transplant in kidney-transplant candidates who have a living human-leukocyte antigen-incompatible (HLAi) donor. We report on the efficacy of semispecific immunoadsorption to allow HLAi kidney transplant in 6 highly sensitized patients.

MATERIALS AND METHODS

We chose immunoadsorption as the apheresis technique coupled to hemodialysis as a means to decrease donor-specific alloantibodies in kidney transplant candidates submitted to a pretransplant desensitization program to remove detrimental antibodies.

RESULTS

Six highly sensitized kidney-transplant patients (5 females), awaiting their first (n = 1) or second (n = 5) kidney transplant from a living donor, were enrolled in this desensitization program. They had 1 (n = 2), 2 (n = 1), 3 (n = 2), or 4 (n = 1) donor-specific alloantibodies; their mean fluorescent intensities at predesensitization ranged from 1200 to 19 000. Each patient underwent between 10 and 16 immunoadsorption sessions. At the time of transplant, donor-specific alloantibodies were undetectable in 2 patients (A24, DR3); donorspecific alloantibodies decreased by > 50% in 8 patients (A11, B44, DR3, DR11, DQ3 thrice, DQ5); donor-specific alloantibodies remained unchanged in 2 patients (B50, DR13); and mean fluorescent intensities were slightly increased in 2 patients (Cw6, DQ8). In the analysis of final outcomes, 2 patients experienced no rejection (1 experienced donor-specific alloantibody elimination, and 1 experienced a > 50% decrease in donor-specific alloantibodies). One patient presented with acute antibody-mediated rejection, which required immunoadsorption sessions and eculizumab therapy (donor-specific alloantibodies between 5000 and 19 000). Two patients presented with subacute antibody-mediated rejection; 1 was treated by plasmapheresis/rituximab therapy, and the other was treated with plasmapheresis/ methylprednisolone pulses. Another patient presented with chronic antibody-mediated rejection, which was treated unsuccessfully with plasmapheresis/rituximab; a tentative of rescue therapy with eculizumab was attempted without success.

CONCLUSIONS

Desensitization of the humanleukocyte antigen using this immunoadsorption procedure effectively reduced or eliminated donorspecific alloantibodies in 71% of patients undergoing kidney transplant, at the time of transplant.

摘要

目的

我们在本中心实施了一项脱敏计划,以使具有人类白细胞抗原不相容(HLAi)活体供体的肾移植候选者能够接受移植。我们报告了半特异性免疫吸附在6例高度致敏患者中实现HLAi肾移植的疗效。

材料与方法

我们选择免疫吸附作为与血液透析相结合的血液分离技术,作为降低接受移植前脱敏计划以去除有害抗体的肾移植候选者中供体特异性同种抗体的一种手段。

结果

6例高度致敏的肾移植患者(5例女性),等待接受来自活体供体的首次(n = 1)或第二次(n = 5)肾移植,被纳入该脱敏计划。他们有1种(n = 2)、2种(n = 1)、3种(n = 2)或4种(n = 1)供体特异性同种抗体;脱敏前其平均荧光强度范围为1200至19000。每位患者接受了10至16次免疫吸附治疗。在移植时,2例患者(A24、DR3)检测不到供体特异性同种抗体;8例患者(A11、B44、DR3、DR11、DQ3三次、DQ5)的供体特异性同种抗体减少>50%;2例患者(B50、DR13)的供体特异性同种抗体保持不变;2例患者(Cw6、DQ8)的平均荧光强度略有增加。在最终结局分析中,2例患者未发生排斥反应(1例经历了供体特异性同种抗体清除,1例供体特异性同种抗体减少>50%)。1例患者出现急性抗体介导的排斥反应,需要进行免疫吸附治疗和使用依库珠单抗(供体特异性同种抗体在5000至19000之间)。2例患者出现亚急性抗体介导的排斥反应;1例接受了血浆置换/利妥昔单抗治疗,另1例接受了血浆置换/甲泼尼龙冲击治疗。另1例患者出现慢性抗体介导的排斥反应,血浆置换/利妥昔单抗治疗无效;尝试使用依库珠单抗进行挽救治疗但未成功。

结论

使用这种免疫吸附程序对人类白细胞抗原进行脱敏,在移植时有效降低或消除了71%接受肾移植患者的供体特异性同种抗体。

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