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儿童肠道移植受者新发供者特异性抗体的抗体清除疗法:为何、何时以及如何进行?单中心经验

Antibody-removal therapies for de novo DSA in pediatric intestinal recipients: Why, when, and how? A single-center experience.

作者信息

Lasa-Lázaro María, Ramos-Boluda Esther, Mancebo Esther, Castro-Panete María José, González-Sacristán Rocío, Serradilla Javier, Andrés-Moreno Ane Miren, Hernández-Oliveros Francisco, Paz-Artal Estela, Talayero Paloma

机构信息

Department of Immunology, University Hospital 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain.

Unit of Intestinal Rehabilitation and Transplant, University Hospital La Paz, Madrid, Spain.

出版信息

Front Pediatr. 2023 Feb 2;10:1074577. doi: 10.3389/fped.2022.1074577. eCollection 2022.

Abstract

BACKGROUND

Donor-specific anti-HLA antibodies (DSA) impact negatively on the outcome of intestinal grafts. Although the use of antibody-removal therapies (ART) is becoming more frequent in the last few years, issues regarding their timing and effectiveness remain under discussion.

METHODS

In the present study, we report our experience with eight ART procedures (based on plasmapheresis, intravenous immunoglobulin, and rituximab) in eight pediatric intestinal and multivisceral transplants with de novo DSA (dnDSA).

RESULTS

ART were performed when dnDSA appeared in two contexts: (1) concomitant with rejection (acute or chronic) or (2) without rejection or any other clinical symptom. Complete DSA removal was observed in seven out of eight patients, showing an effectiveness of 88%. In the group treated for dnDSA without clinical symptoms, the success rate was 100%, with complete DSA removal and without rejection afterward. A shorter time between DSA detection and ART performance appeared as a significant factor for the success of the therapy ( = 0.0002). DSA against HLA-A and DQ alleles were the most resistant to ART, whereas anti-DR DSA were the most sensitive. In addition, the 8-year allograft survival rate in recipients undergoing ART was similar to that in those without DSA, being significantly lower in non-treated DSA-positive recipients ( = 0.013).

CONCLUSION

The results confirm the effectiveness of ART in terms of DSA removal and allograft survival and encourage its early use even in the absence of clinical symptoms.

摘要

背景

供者特异性抗人白细胞抗原抗体(DSA)对肠道移植的预后有负面影响。尽管在过去几年中抗体清除疗法(ART)的使用越来越频繁,但其时机和有效性问题仍在讨论中。

方法

在本研究中,我们报告了8例小儿肠道和多脏器移植患者发生新发DSA(dnDSA)时接受8种ART程序(基于血浆置换、静脉注射免疫球蛋白和利妥昔单抗)的经验。

结果

ART在两种情况下进行,即dnDSA出现时:(1)与排斥反应(急性或慢性)同时发生,或(2)无排斥反应或任何其他临床症状。8例患者中有7例DSA完全清除,有效率为88%。在无临床症状的dnDSA治疗组中,成功率为100%,DSA完全清除且之后无排斥反应。DSA检测与ART实施之间的时间较短是治疗成功的一个重要因素(P = 0.0002)。针对HLA - A和DQ等位基因的DSA对ART最具抗性,而抗DR DSA最敏感。此外,接受ART的受者8年移植物存活率与无DSA的受者相似,未治疗的DSA阳性受者的存活率显著较低(P = 0.013)。

结论

结果证实了ART在清除DSA和移植物存活方面的有效性,并鼓励即使在没有临床症状的情况下也尽早使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c4/9932897/f6fbcc0ddddf/fped-10-1074577-g001.jpg

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