Redondo Natalia, Rodríguez-Goncer Isabel, Ruiz-Merlo Tamara, López-Medrano Francisco, González Esther, Polanco Natalia, Hernández-Vicente Ana, San Juan Rafael, Andrés Amado, Aguado José María, Fernández-Ruiz Mario
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
Transpl Int. 2025 May 21;38:14648. doi: 10.3389/ti.2025.14648. eCollection 2025.
Herpesviruses are able to modulate adaptive T-cell-mediated responses to establish latency within the host. Reactivation of herpes simplex virus (HSV)-1/2 and varicella zoster virus (VZV) is a frequent and potentially serious complication among kidney transplant recipients (KTRs). The ability of clinical criteria to identify KTRs at increased risk of α-herpesvirus (HSV/VZV) infection is limited. We investigated the effect of two single nucleotide polymorphisms (SNPs) in the cytotoxic T-lymphocyte antigen 4 gene in a single-center cohort of 204 KTRs. After a median follow-up of 3.1 years, 34 of them (16.7%) experienced 22 episodes of zoster and 15 episodes of HSV-1/2 infection. Homozygous carriers of the minor allele of rs231775 had a higher cumulative incidence of α-herpesvirus infection (23.5% for GG versus 7.6% for AA/AG carriers; -value = 0.011) and a lower infection-free survival (log-rank -value = 0.037). After multivariable adjustment by clinical factors (including use of valganciclovir prophylaxis and acute rejection as time-dependent variables), the GG genotype of (rs231775) SNP was associated to the study outcome (adjusted hazard ratio: 3.21; 95% confidence interval: 1.44-7.16). In conclusion, genetic polymorphisms in the co-inhibitory T-cell receptor CTLA-4 may be detrimental for the immune control of latent HSV/VZV infection in KTRs.
疱疹病毒能够调节适应性T细胞介导的反应，从而在宿主体内建立潜伏状态。单纯疱疹病毒（HSV）-1/2和水痘带状疱疹病毒（VZV）的再激活是肾移植受者（KTRs）中常见且可能严重的并发症。临床标准识别α疱疹病毒（HSV/VZV）感染风险增加的KTRs的能力有限。我们在一个包含204名KTRs的单中心队列中研究了细胞毒性T淋巴细胞抗原4基因中的两个单核苷酸多态性（SNP）的影响。中位随访3.1年后，其中34人（16.7%）经历了22次带状疱疹发作和15次HSV-1/2感染发作。rs231775次要等位基因的纯合携带者α疱疹病毒感染的累积发生率更高（GG为23.5%，AA/AG携带者为7.6%；P值 = 0.011），无感染生存期更低（对数秩检验P值 = 0.037）。在通过临床因素进行多变量调整后（包括使用缬更昔洛韦预防和将急性排斥作为时间依赖性变量），rs231775 SNP的GG基因型与研究结果相关（调整后的风险比：3.21；95%置信区间：1.44 - 7.16）。总之，共抑制性T细胞受体CTLA - 4中的基因多态性可能对KTRs中潜伏性HSV/VZV感染的免疫控制不利。
