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利妥昔单抗/静脉注射免疫球蛋白脱敏方案在肾移植中的局限性;这比时间的治愈力更好吗?

Limitations of rituximab/IVIg desensitization protocol in kidney transplantation; is this better than a tincture of time?

作者信息

Kozlowski Tomasz, Andreoni Kenneth

机构信息

Department of Surgery, University of North Carolina at Chapel Hill, 27599, USA.

出版信息

Ann Transplant. 2011 Apr-Jun;16(2):19-25. doi: 10.12659/aot.881860.

DOI:10.12659/aot.881860
PMID:21716181
Abstract

BACKGROUND

A plasmapheresis-free protocol for desensitization of donor kidney transplant candidates with high Calculated Panel Reactive Antibody (CPRA) was initiated at our center. The protocol was adopted from previously published work by Vo, Jordan et al.

MATERIAL/METHODS: Five patients with CPRA of 94 ± 18%, awaiting kidney transplant from living or deceased donors received rituximab (1 g × 2 doses) and intravenous immunoglobulin (IVIG 2 g/kg × 2 doses) without plasmapheresis. Levels of donor specific antibodies (DSA) and T/B cell crossmatches were followed using solid phase flow cytometry.

RESULTS

Three out of 5 patients were sensitized only to Class II HLA antigens. All patients had very high levels of alloantibodies before initiation of the treatment. All of the candidates initially demonstrated reduced levels of HLA antibody, but statistical significance was only obtained in one patient Class II antibody and in another only for Class I. Depletion was transient with observed antibody rebound. Rituximab effectively depleted CD20 cells in peripheral blood. None of the patients were transplanted due to persistently high levels of antibody and strong positive flow cytometry crossmatches. Under this protocol, reduction of HLA antibodies in patients with high levels was insufficient.

CONCLUSIONS

Highly allo-sensitized patients with a CPRA above 85% may not benefit from a combination of rituximab-IVIG alone. The previously published protocol does not help all patients achieve an acceptable crossmatch. An individualized approach to the treatment of highly sensitized patients is still required.

摘要

背景

我们中心启动了一项针对高计算群体反应性抗体(CPRA)的供体肾移植候选者脱敏的无血浆置换方案。该方案借鉴了Vo、Jordan等人先前发表的研究成果。

材料/方法:5例CPRA为94±18%、等待活体或尸体供体肾移植的患者接受了利妥昔单抗(1g×2剂)和静脉注射免疫球蛋白(IVIG 2g/kg×2剂),未进行血浆置换。使用固相流式细胞术监测供体特异性抗体(DSA)水平和T/B细胞交叉配型。

结果

5例患者中有3例仅对II类HLA抗原致敏。所有患者在治疗开始前均有非常高的同种抗体水平。所有候选者最初均显示HLA抗体水平降低,但仅1例患者的II类抗体和另1例患者的I类抗体具有统计学意义。抗体耗竭是短暂的,观察到抗体反弹。利妥昔单抗有效地清除了外周血中的CD20细胞。由于抗体水平持续较高和流式细胞术交叉配型呈强阳性,所有患者均未进行移植。在此方案下,高水平患者的HLA抗体减少不足。

结论

CPRA高于85%的高度同种致敏患者可能无法仅从利妥昔单抗-IVIG联合治疗中获益。先前发表的方案并不能帮助所有患者实现可接受的交叉配型。仍需要对高度致敏患者采取个体化治疗方法。

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