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肾移植受者循环中抗供体特异性HLA抗体及其特征(包括C1q结合能力)与长期肾移植结局的相关性

Association of Circulating Anti-HLA Donor-Specific Antibodies and Their Characteristics, including C1q-Binding Capacity, in Kidney Transplant Recipients with Long-Term Renal Graft Outcomes.

作者信息

Gniewkiewicz Michal, Czerwinska Katarzyna, Zielniok Katarzyna, Durlik Magdalena

机构信息

Department of Transplantation Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Poland.

Department of Clinical Immunology, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Poland.

出版信息

J Clin Med. 2023 Feb 7;12(4):1312. doi: 10.3390/jcm12041312.

DOI:10.3390/jcm12041312
PMID:36835848
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9962721/
Abstract

Post-transplant antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) monitoring in kidney transplant recipients remains unclear and is currently under investigation. The pathogenicity of anti-HLA DSAs is determined by antibody classes, specificity, mean fluorescent intensity (MFI), C1q-binding capacity, and IgG subclasses. The aim of this study was to investigate the association of circulating DSAs and their characteristics with renal allograft long-term outcomes. The study included 108 consecutive patients from our transplant center who underwent kidney allograft biopsy between November 2018 and November 2020, 3 to 24 months after kidney transplantation. At the time of biopsy, patients' sera were collected for analysis of anti-HLA DSAs. Patients were followed for a median time of 39.0 months (Q1-Q3, 29.8-45.0). Detection of anti-HLA DSAs at the time of biopsy (HR = 5.133, 95% CI 2.150-12.253, = 0.0002) and their C1q-binding capacity (HR = 14.639, 95% CI 5.320-40.283, ≤ 0.0001) were independent predictors of the composite of sustained 30% reduction from estimated glomerular filtration rate or death-censored graft failure. Identification of anti-HLA DSAs and their C1q-binding capacity could be useful in identifying kidney transplant recipients at risk for inferior renal allograft function and graft failure. Analysis of C1q is noninvasive, accessible, and should be considered in clinical practice in post-transplant monitoring.

摘要

肾移植受者移植后抗人白细胞抗原供体特异性抗体(抗HLA DSA)监测仍不明确,目前正在研究中。抗HLA DSA的致病性由抗体类别、特异性、平均荧光强度(MFI)、C1q结合能力和IgG亚类决定。本研究的目的是探讨循环DSA及其特征与肾移植长期预后的关系。该研究纳入了我们移植中心108例连续患者,他们在2018年11月至2020年11月期间,肾移植后3至24个月接受了肾移植活检。在活检时,收集患者血清以分析抗HLA DSA。患者的中位随访时间为39.0个月(第一四分位数-第三四分位数,29.8-45.0)。活检时检测到抗HLA DSA(HR = 5.133,95%CI 2.150-12.253,P = 0.0002)及其C1q结合能力(HR = 14.639,95%CI 5.320-40.283,P≤0.0001)是估计肾小球滤过率持续降低30%或死亡删失的移植失败复合结局的独立预测因素。识别抗HLA DSA及其C1q结合能力可能有助于识别肾移植受者发生肾移植功能低下和移植失败的风险。C1q分析是非侵入性的、可获得的,在移植后监测的临床实践中应予以考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5bb/9962721/b42ac6a1cb2d/jcm-12-01312-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5bb/9962721/b42ac6a1cb2d/jcm-12-01312-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5bb/9962721/b42ac6a1cb2d/jcm-12-01312-g001.jpg

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本文引用的文献

1
Clinical recommendations for posttransplant assessment of anti-HLA (Human Leukocyte Antigen) donor-specific antibodies: A Sensitization in Transplantation: Assessment of Risk consensus document.移植后抗 HLA(人类白细胞抗原)供体特异性抗体评估的临床建议:致敏移植:风险评估共识文件。
Am J Transplant. 2023 Jan;23(1):115-132. doi: 10.1016/j.ajt.2022.11.013. Epub 2023 Jan 11.
2
Strategies to Overcome HLA Sensitization and Improve Access to Retransplantation after Kidney Graft Loss.克服HLA致敏并改善肾移植失功后再次移植机会的策略
J Clin Med. 2022 Sep 28;11(19):5753. doi: 10.3390/jcm11195753.
3
Complement-Binding Donor-Specific Anti-HLA Antibodies: Biomarker for Immunologic Risk Stratification in Pediatric Kidney Transplantation Recipients.
补体结合供者特异性抗 HLA 抗体:儿科肾移植受者免疫风险分层的生物标志物。
Transpl Int. 2022 Mar 16;35:10158. doi: 10.3389/ti.2021.10158. eCollection 2022.
4
Microvascular Inflammation of the Renal Allograft: A Reappraisal of the Underlying Mechanisms.移植肾的微血管炎症:对潜在机制的再评估。
Front Immunol. 2022 Mar 22;13:864730. doi: 10.3389/fimmu.2022.864730. eCollection 2022.
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The Clinical Impact of Anti-HLA Donor Specific Antibody Detection Through First Year Screening on Stable Kidney Transplant Recipients.通过第一年的筛查检测抗 HLA 供体特异性抗体对稳定肾移植受者的临床影响。
Transpl Int. 2022 Mar 17;35:10094. doi: 10.3389/ti.2022.10094. eCollection 2022.
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Accuracy of virtual crossmatch (VXM) prediction of physical crossmatch (PXM) results of donor specific antibody (DSA) in routine pretransplant settings-a single-center experience.常规移植前环境中供者特异性抗体(DSA)虚拟交叉配型(VXM)对物理交叉配型(PXM)结果预测的准确性:单中心经验。
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Transpl Immunol. 2022 Jun;72:101566. doi: 10.1016/j.trim.2022.101566. Epub 2022 Mar 4.
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Donor-derived Cell-free DNA Complements De Novo Class II DSA in Detecting Late Alloimmune Injury Post Kidney Transplantation.供体来源的游离DNA在检测肾移植后晚期同种免疫损伤中补充了新生的Ⅱ类供者特异性抗体。
Transplant Direct. 2022 Jan 26;8(2):e1285. doi: 10.1097/TXD.0000000000001285. eCollection 2022 Feb.