Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Nephrol Dial Transplant. 2012 May;27(5):2122-9. doi: 10.1093/ndt/gfr610. Epub 2011 Nov 15.
Recipient desensitization using blood group (BG)-specific immunoadsorption (ABO-IA) has proven to enable successful kidney transplantation across major ABO barriers. In this context, the efficiency of non-antigen-specific (semiselective) IA adsorbers has not yet been established. The objective of our study was to quantify anti-A/B antibody depletion by protein A-, peptide ligand- and anti-human immunoglobulin-based semiselective IA in comparison to ABO-IA.
Eight ABO-IA-treated transplant candidates and 39 patients subjected to semiselective IA for a variety of different indications outside the context of ABO-incompatible transplantation were included. Antibody patterns (IgG, IgG1-4 subclasses, IgM, C4d-fixing reactivities) were analysed applying conventional agglutination testing and flow cytometry.
As assessed by sensitive flow cytometric antibody detection, ABO-IA-based desensitization led to a profound even though often incomplete reduction of anti-A/B reactivities. Persistent complement- or non-complement-fixing reactivities, however, were not associated with transplant rejection or capillary C4d deposition. Single sessions of semiselective IA turned out to be more effective than ABO-IA in decreasing levels of anti-A/B IgG [median reduction to 28 versus 59% (ABO-IA) of baseline values, P < 0.001). In contrast, BG-specific IgM (74 versus 30%, P < 0.001) and IgG3 (72 versus 42%, P < 0.05) were reduced to a lesser extent, without differences between tested adsorber types. Analysis of four consecutive IA sessions revealed that inferior efficiency could not be overcome by serial treatment.
Our observation of limited adsorption capacities regarding distinct BG-specific Ig (sub)classes suggests caution in applying semiselective IA techniques in ABO-incompatible kidney transplantation.
使用血型(BG)特异性免疫吸附(ABO-IA)进行受体致敏已被证明可在主要 ABO 障碍下实现成功的肾移植。在这种情况下,非抗原特异性(半选择性)IA 吸附剂的效率尚未确定。我们的研究目的是定量比较基于蛋白 A、肽配体和抗人免疫球蛋白的半选择性 IA 与 ABO-IA 对抗-A/B 抗体的清除效率。
纳入了 8 名接受 ABO-IA 治疗的移植候选人和 39 名因各种不同适应症而接受半选择性 IA 治疗的患者,这些适应症与 ABO 不相容移植无关。应用常规凝集试验和流式细胞术分析抗体模式(IgG、IgG1-4 亚类、IgM、C4d 结合活性)。
通过敏感的流式细胞术抗体检测评估,基于 ABO-IA 的脱敏导致抗-A/B 反应性明显降低,尽管常常不完全。然而,持续的补体或非补体结合反应性与移植排斥或毛细血管 C4d 沉积无关。单次半选择性 IA 治疗比 ABO-IA 更有效地降低抗-A/B IgG 水平[中位数降低至基线值的 28%对 59%(ABO-IA),P < 0.001)。相比之下,BG 特异性 IgM(74%对 30%,P < 0.001)和 IgG3(72%对 42%,P < 0.05)的降低程度较小,但不同测试吸附剂类型之间无差异。对 4 次连续 IA 治疗的分析表明,较差的效率无法通过连续治疗来克服。
我们对特定 BG 特异性 Ig(亚)类别的吸附能力有限的观察结果表明,在 ABO 不相容性肾移植中应用半选择性 IA 技术时应谨慎。