{"title":"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","authors":"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","doi":"10.1111/tid.70108","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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/mm<sup>3</sup>) 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>NUDT15 variants increase the risk of early neutropenia during VGCV prophylaxis in lung transplant recipients.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e70108"},"PeriodicalIF":2.6000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"NUDT15 Genetic Polymorphism as a Risk Factor for Early Neutropenia During Valganciclovir Prophylaxis in Lung Transplant Patients.\",\"authors\":\"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\",\"doi\":\"10.1111/tid.70108\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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/mm<sup>3</sup>) 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>NUDT15 variants increase the risk of early neutropenia during VGCV prophylaxis in lung transplant recipients.</p>\",\"PeriodicalId\":23318,\"journal\":{\"name\":\"Transplant Infectious Disease\",\"volume\":\" \",\"pages\":\"e70108\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Transplant Infectious Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/tid.70108\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplant Infectious Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/tid.70108","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
NUDT15 Genetic Polymorphism as a Risk Factor for Early Neutropenia During Valganciclovir Prophylaxis in Lung Transplant Patients.
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
