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供体特异性HLA-DQ抗体可能导致心脏移植后移植物预后不良。

Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after heart transplantation.

作者信息

Omrani Osama, Alawwami Moheeb, Buraiki Jehad, Selimovic Nedim

机构信息

Nedim Selimovic, Department of Cardiology, Angereds Narsjukhus,, SE-424 Angered, Sweden,

出版信息

Ann Saudi Med. 2018 Mar-Apr;38(2):97-104. doi: 10.5144/0256-4947.2018.97.

DOI:10.5144/0256-4947.2018.97
PMID:29620542
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6074361/
Abstract

BACKGROUND

HLA-DQ donor-specific antibodies (DSA) are implicated in allograft dysfunction after renal and lung transplantation. Limited data exists on the impact of HLA-DQ antibodies on heart transplant patients.

OBJECTIVE

To investigate the impact of DSA formation on allograft function and outcomes in heart transplant patients.

DESIGN

Retrospective cohort study.

SETTING

Collating post-transplantation patient data from computerized database in a tertiary hospital in Riyadh, Saudi Arabia from January 2006 to October 2014.

PATIENTS AND METHODS

We excluded recipients with positive preoperative complement-dependent-cytotoxicity crossmatch grafts and those with preformed DSA. Anti-HLA antibodies were identified using Luminex-based assay in sera collected before transplantation with a routine endomyocardial biopsy the first year and then annually.

MAIN OUTCOME MEASURES

Primary outcome measures were all-cause mortality, development of antibody mediated rejection, treated acute cellular rejection (ACR) and cardiac allograft vasculopathy (CAV).

SAMPLE SIZE

127 patients.

RESULTS

DSA formation occurred in 43/127 (34%), with 33/43 (77%) targeting HLA-DQ antigens alone (n=7) or in combination with -DR, -A or B antibodies (n=26). Most (76%) were male and the mean (SD) age was 36 (14) years. Ten patients developed -A, -B or -DR antibodies without -DQ antibodies also present. Treated ACR (P=.011), reduced left ventricular ejection fraction (P less than .001), CAV development (P=.003), and all-cause mortality (P=.01) were all significantly more prevalent in the DSA-positive cohort.

CONCLUSION

HLA-DQ donor-specific antibodies were the most common type detected and may play a significant role in poor outcomes post-cardiac transplantation. This emphasizes the importance of HLA-DQ matching and monitoring for DSA formation in order to minimize post-transplantation immunological risk.

LIMITATIONS

Retrospective design comes with inherent biases, results from single institute, with a particularly young cohort.

CONFLICT OF INTEREST

None.

摘要

背景

HLA - DQ供者特异性抗体(DSA)与肾移植和肺移植后的移植物功能障碍有关。关于HLA - DQ抗体对心脏移植患者影响的数据有限。

目的

研究DSA形成对心脏移植患者移植物功能和预后的影响。

设计

回顾性队列研究。

背景

整理2006年1月至2014年10月沙特阿拉伯利雅得一家三级医院计算机数据库中的移植后患者数据。

患者和方法

我们排除了术前补体依赖细胞毒性交叉配型阳性的受者以及那些预先存在DSA的受者。在移植前采集的血清中使用基于Luminex的检测方法鉴定抗HLA抗体,第一年进行常规心内膜心肌活检,之后每年进行一次。

主要观察指标

主要观察指标为全因死亡率、抗体介导排斥反应的发生、治疗的急性细胞排斥反应(ACR)和心脏移植物血管病变(CAV)。

样本量

127例患者。

结果

43/127(34%)发生了DSA形成,其中33/43(77%)仅针对HLA - DQ抗原(n = 7)或与 - DR、- A或B抗体联合(n = 26)。大多数(76%)为男性,平均(标准差)年龄为36(14)岁。10例患者产生了 - A、- B或 - DR抗体,但不存在 - DQ抗体。在DSA阳性队列中,治疗的ACR(P = 0.011)、左心室射血分数降低(P < 0.001)、CAV发生(P = 0.003)和全因死亡率(P = 0.01)均显著更常见。

结论

HLA - DQ供者特异性抗体是检测到的最常见类型,可能在心脏移植后不良预后中起重要作用。这强调了HLA - DQ配型和监测DSA形成的重要性,以尽量减少移植后免疫风险。

局限性

回顾性设计存在固有偏差,结果来自单一机构,且队列特别年轻。

利益冲突

无。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/663c/6074361/a0a21fe502a4/asm-2-97f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/663c/6074361/36bbc6e6466a/asm-2-97f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/663c/6074361/f102567f555e/asm-2-97f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/663c/6074361/a0a21fe502a4/asm-2-97f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/663c/6074361/36bbc6e6466a/asm-2-97f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/663c/6074361/f102567f555e/asm-2-97f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/663c/6074361/a0a21fe502a4/asm-2-97f3.jpg

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本文引用的文献

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Clin Transplant. 2017 Nov;31(11). doi: 10.1111/ctr.13121. Epub 2017 Oct 15.
2
De novo DQ donor-specific antibodies are associated with worse outcomes compared to non-DQ de novo donor-specific antibodies following heart transplantation.与心脏移植后非DQ新发供者特异性抗体相比,新发DQ供者特异性抗体与更差的预后相关。
Clin Transplant. 2017 Apr;31(4). doi: 10.1111/ctr.12924. Epub 2017 Mar 5.
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HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients.
肾移植受者中的HLA - DQ错配与排斥反应
Clin J Am Soc Nephrol. 2016 May 6;11(5):875-883. doi: 10.2215/CJN.11641115. Epub 2016 Mar 31.
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The use of circulating donor specific antibody to predict biopsy diagnosis of antibody-mediated rejection and to provide prognostic value after heart transplantation in children.循环供体特异性抗体用于预测儿童心脏移植后抗体介导排斥反应的活检诊断和提供预后价值。
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The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Heart Transplantation Report--2015; Focus Theme: Early Graft Failure.国际心肺移植学会登记处:第三十二次成人心脏移植官方报告——2015年;重点主题:早期移植物功能衰竭
J Heart Lung Transplant. 2015 Oct;34(10):1244-54. doi: 10.1016/j.healun.2015.08.003. Epub 2015 Aug 28.
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