NUDT15 Genetic Polymorphism as a Risk Factor for Early Neutropenia During Valganciclovir Prophylaxis in Lung Transplant Patients.

IF 2.6 4区医学 Q3 IMMUNOLOGY

Transplant Infectious Disease Pub Date : 2025-09-18 DOI:10.1111/tid.70108

Yurie Katsube, Keisuke Umemura, Yuzuki Urabe, Miori Ono, Yoshiki Katada, Daiki Hira, Akihiro Ohsumi, Daisuke Nakajima, Masahiro Tsuda, Shunsaku Nakagawa, Tomoyuki Mizuno, Miki Nagao, Hiroshi Date, Tomohiro Terada

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引用次数: 0

Abstract

Background: Valganciclovir (VGCV) prophylaxis effectively prevents cytomegalovirus infection in lung transplant patients. However, VGCV-induced neutropenia causes early cessation. Nucleoside diphosphate-linked moiety X-type motif (NUDT) 15 degrades the ganciclovir (GCV) triphosphate, an active metabolite. We assessed the effects of NUDT15 variants on neutropenia and VGCV cessation in recipients of lung transplants.

Methods: We recruited 28 patients who had received lung transplants and VGCV prophylaxis and genotyped NUDT15 exons 1-3 using Sanger sequencing. Neutrophil counts were monitored from 1 month to 1 year in the wild-type and NUDT15 reduced-function variant groups. Cumulative incidences of neutropenia (< 1500/mm³) and neutropenia-related cessation within 1 year, including late-onset neutropenia, were assessed using Kaplan-Meier analysis. A subgroup analysis was conducted focusing on patients with stable renal function, the primary route of excretion for GCV.

Results: Of the 28 patients, nine carried NUDT15 variants (Arg139Cys, Val18Ile, Val18_Val19insGlyVal, Arg139Cys/Val18Ile). The neutrophil count nadir within 1 month of treatment was lower in the NUDT15-variant group than in the wild-type group. A higher incidence of neutropenia and VGCV cessation was observed in the NUDT15-variant group, but without statistical significance. Among 13 patients with stable renal function, all four in the NUDT15-variant group developed neutropenia and cessation within 60 days, compared with two of nine in the wild-type group. Covariance analysis showed that NUDT15 variants were associated with decreased neutrophil counts, independent of GCV trough concentration.

Conclusion: NUDT15 variants increase the risk of early neutropenia during VGCV prophylaxis in lung transplant recipients.

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NUDT15基因多态性作为肺移植患者缬更昔洛韦预防期间早期中性粒细胞减少的危险因素

背景：缬更昔洛韦（VGCV）预防能有效预防肺移植患者巨细胞病毒感染。然而，vgcv诱导的中性粒细胞减少导致早期戒烟。核苷二磷酸连接片段x型基序（NUDT） 15降解活性代谢物更昔洛韦（GCV）三磷酸。我们评估了NUDT15变异对肺移植受者中性粒细胞减少和VGCV停止的影响。方法：我们招募了28例接受肺移植和VGCV预防的患者，并使用Sanger测序对NUDT15外显子1-3进行了基因分型。在野生型和NUDT15功能变异型组中监测中性粒细胞计数从1个月到1年。使用Kaplan-Meier分析评估1年内中性粒细胞减少(3)和中性粒细胞减少相关停止的累积发生率，包括迟发性中性粒细胞减少。对肾功能稳定的患者进行亚组分析，肾功能稳定是GCV的主要排泄途径。结果：28例患者中，9例携带NUDT15变体（Arg139Cys, Val18Ile, Val18_Val19insGlyVal, Arg139Cys/Val18Ile）。nut15变异组治疗1个月内中性粒细胞计数最低点低于野生型组。nudt15变异组中性粒细胞减少和VGCV停止的发生率较高，但无统计学意义。在13名肾功能稳定的患者中，nudt15变异组的4名患者均在60天内出现中性粒细胞减少并停止，而野生型组的9名患者中只有2名。协方差分析显示，NUDT15变异与中性粒细胞计数下降相关，与GCV谷浓度无关。结论：NUDT15变异增加了肺移植受者在VGCV预防期间早期中性粒细胞减少的风险。

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

Transplant Infectious Disease 医学-传染病学

CiteScore

5.30

自引率

7.70%

发文量

210

审稿时长

4-8 weeks

期刊介绍： Transplant Infectious Disease has been established as a forum for presenting the most current information on the prevention and treatment of infection complicating organ and bone marrow transplantation. The point of view of the journal is that infection and allograft rejection (or graft-versus-host disease) are closely intertwined, and that advances in one area will have immediate consequences on the other. The interaction of the transplant recipient with potential microbial invaders, the impact of immunosuppressive strategies on this interaction, and the effects of cytokines, growth factors, and chemokines liberated during the course of infections, rejection, or graft-versus-host disease are central to the interests and mission of this journal. Transplant Infectious Disease is aimed at disseminating the latest information relevant to the infectious disease complications of transplantation to clinicians and scientists involved in bone marrow, kidney, liver, heart, lung, intestinal, and pancreatic transplantation. The infectious disease consequences and concerns regarding innovative transplant strategies, from novel immunosuppressive agents to xenotransplantation, are very much a concern of this journal. In addition, this journal feels a particular responsibility to inform primary care practitioners in the community, who increasingly are sharing the responsibility for the care of these patients, of the special considerations regarding the prevention and treatment of infection in transplant recipients. As exemplified by the international editorial board, articles are sought throughout the world that address both general issues and those of a more restricted geographic import.