Functional Natural Killer-cell Genetics and Microvascular Inflammation After Kidney Transplantation: An Observational Cohort Study.

IF 5.3 2区医学 Q1 IMMUNOLOGY

Transplantation Pub Date : 2024-10-15 DOI:10.1097/TP.0000000000005228

Matthias Diebold, Hannes Vietzen, Martina Schatzl, Katharina A Mayer, Susanne Haindl, Andreas Heinzel, Philip Hittmeyer, Carsten T Herz, Helmut Hopfer, Thomas Menter, Laura M Kühner, Sarah M Berger, Elisabeth Puchhammer-Stöckl, Konstantin Doberer, Jürg Steiger, Stefan Schaub, Georg A Böhmig

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引用次数: 0

Abstract

Background: Recent evidence highlights the pivotal role of natural killer (NK) cells in allograft rejection.

Methods: We explored associations of missing self and gene polymorphisms determining the phenotype and/or functionality of NK cells with microvascular inflammation (MVI) in a single-center cohort of 507 consecutive kidney transplant recipients. Patients were genotyped for killer cell Ig-like receptors and polymorphisms in 4 selected genes (FCGR3AV/F158 [rs396991], KLRC2wt/del, KLRK1HNK/LNK [rs1049174], and rs9916629-C/T).

Results: MVI was detected in 69 patients (13.6%). In a proportional odds model, the KLRC2del/del variant reduced MVI risk (odds ratio [OR] 0.26; 95% confidence interval [CI], 0.05-0.93; P = 0.037) independent of donor-specific antibodies, HLA class II eplet mismatch, and number of biopsies. Conversely, missing self (OR 1.40; 95% CI, 1.08-1.80; P = 0.011) and the rs9916629 T/T gene variant increased the risk (OR 1.70; 95% CI, 1.08-2.68; P = 0.021). Graft loss tended to be more frequent among patients with missing self ≥2 (hazard ratio 1.97; 95% CI, 0.89-4.37; P = 0.097), without influence on estimated glomerular filtration trajectories. FCGR3A variants were associated with MVI only in patients with preformed and/or de novo donor-specific antibodies (OR 4.14; 95% CI, 0.99-17.47; P = 0.052).

Conclusions: Missing self and NK-cell genetics may contribute to MVI, underscoring the important role of NK cells in transplant rejection.

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功能性天然杀伤细胞遗传与肾移植后的微血管炎症：一项观察性队列研究

背景：最近有证据表明，自然杀伤细胞（NK）在异体移植排斥反应中起着关键作用：最近的证据表明，自然杀伤（NK）细胞在异体移植排斥反应中起着关键作用：我们在一个由 507 名连续肾移植受者组成的单中心队列中探讨了决定 NK 细胞表型和/或功能的自身缺失和基因多态性与微血管炎症（MVI）的关联。对患者的杀伤细胞 Ig 样受体和 4 个选定基因（FCGR3AV/F158 [rs396991]、KLRC2wt/del、KLRK1HNK/LNK [rs1049174] 和 rs9916629-C/T）的多态性进行了基因分型：结果：69 名患者（13.6%）检测出 MVI。在比例赔率模型中，KLRC2del/del 变异降低了 MVI 风险（赔率比 [OR] 0.26；95% 置信区间 [CI]，0.05-0.93；P = 0.037），不受供体特异性抗体、HLA II 类 eplet 错配和活检次数的影响。相反，自身缺失（OR 1.40；95% CI，1.08-1.80；P = 0.011）和 rs9916629 T/T 基因变异会增加风险（OR 1.70；95% CI，1.08-2.68；P = 0.021）。在自我缺失≥2的患者中，移植物丢失的频率更高（危险比 1.97；95% CI，0.89-4.37；P = 0.097），但对估计的肾小球滤过轨迹没有影响。FCGR3A变异仅与预先形成和/或从头产生供体特异性抗体的患者的MVI相关（OR 4.14；95% CI，0.99-17.47；P = 0.052）：结论：缺失的自身和NK细胞遗传学可能会导致MVI，强调了NK细胞在移植排斥中的重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplantation 医学-免疫学

CiteScore

8.50

自引率

11.30%

发文量

1906

审稿时长

1 months

期刊介绍： The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year. Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal. Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed. The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.