肾移植后功能性自然杀伤细胞遗传学与微血管炎症：一项观察性队列研究
Functional Natural Killer-cell Genetics and Microvascular Inflammation After Kidney Transplantation: An Observational Cohort Study.
作者信息
Diebold Matthias, Vietzen Hannes, Schatzl Martina, Mayer Katharina A, Haindl Susanne, Heinzel Andreas, Hittmeyer Philip, Herz Carsten T, Hopfer Helmut, Menter Thomas, Kühner Laura M, Berger Sarah M, Puchhammer-Stöckl Elisabeth, Doberer Konstantin, Steiger Jürg, Schaub Stefan, Böhmig Georg A
机构信息
Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
出版信息
Transplantation. 2025 May 1;109(5):860-870. doi: 10.1097/TP.0000000000005228. Epub 2025 Apr 17.
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.
背景
近期证据凸显了自然杀伤（NK）细胞在同种异体移植排斥反应中的关键作用。
方法
我们在一个由507例连续肾移植受者组成的单中心队列中，探究了“缺失自我”以及决定NK细胞表型和/或功能的基因多态性与微血管炎症（MVI）之间的关联。对患者进行杀伤细胞免疫球蛋白样受体以及4个选定基因（FCGR3AV/F158 [rs396991]、KLRC2wt/del、KLRK1HNK/LNK [rs1049174]和rs9916629-C/T）的多态性基因分型。
结果
69例患者（13.6%）检测到MVI。在比例优势模型中，KLRC2del/del变异降低了MVI风险（优势比[OR] 0.26；95%置信区间[CI]，0.05 - 0.93；P = 0.037），独立于供体特异性抗体、HLA II类表位错配和活检次数。相反，“缺失自我”（OR 1.40；95% CI，1.08 - 1.80；P = 0.011）和rs9916629 T/T基因变异增加了风险（OR 1.70；95% CI，1.08 - 2.68；P = 0.021）。“缺失自我”≥2的患者中移植肾丢失往往更频繁（风险比1.97；95% CI，0.89 - 4.37；P = 0.097），对估计的肾小球滤过轨迹无影响。FCGR3A变异仅在有预先形成的和/或新发供体特异性抗体的患者中与MVI相关（OR 4.14；95% CI，0.99 - 17.47；P = 0.052）。
结论
“缺失自我”和NK细胞遗传学可能导致MVI，强调了NK细胞在移植排斥反应中的重要作用。
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