酶联免疫斑点试验作为评估和监测接受抢先抗病毒治疗的肾移植受者巨细胞病毒感染的补充方法:单中心经验
Enzyme-Linked Immunospot Assay as a Complementary Method to Assess and Monitor Cytomegalovirus Infection in Kidney Transplant Recipients on Pre-emptive Antiviral Therapy: A Single-Center Experience.
作者信息
Favi E, Santangelo R, Iesari S, Morandi M, Marcovecchio G E, Trecarichi E M, Salerno M P, Ferraresso M, Citterio F, Romagnoli J
机构信息
Kidney Transplantation, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Microbiology, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy.
出版信息
Transplant Proc. 2017 Oct;49(8):1766-1772. doi: 10.1016/j.transproceed.2017.07.001.
BACKGROUND
Cytomegalovirus (CMV) disease represents a major cause of post-transplantation morbidity and mortality. To estimate the risk of infection and monitor response to antiviral therapy, current guidelines suggest combination of viral load monitoring with direct assessment of CMV-specific immune response. We used enzyme-linked immunospot (ELISpot) for the evaluation of CMV-specific T-cell response in kidney transplant recipients with CMV viremia and investigated how information gained could help manage CMV infection.
METHODS
Seventeen patients on pre-emptive antiviral therapy and CMV quantitative polymerase chain reaction (qPCR) ≥500 copies/mL (first episode after transplantation) were assessed using ELISpot and divided into Weak (9 patients with baseline ELISpot <25 spot-forming colonies [SFCs]/200,000 peripheral blood mononuclear cells [PBMCs]) and Strong Responders (8 patients with baseline ELISpot ≥25 SFCs/200,000 PBMCs). CMV-specific T-cell response, infection severity, viral load, and antiviral therapy were prospectively recorded and compared between groups at 1, 2, and 24 months of follow-up.
RESULTS
Demographic and transplant characteristics of Weak and Strong Responders were similar. No episodes of CMV disease were observed. Weak Responders were more likely to experience CMV syndrome (56% vs 36.5%) and late virus reactivation (56% vs 25%) than Strong Responders. Weak Responders showed higher baseline median viral loads (19,700 vs 9265 copies/mL) and needed antiviral therapy for longer (179 vs 59.5 days). T-cell response showed 2 main patterns: early and delayed.
CONCLUSIONS
ELISpot provides prognostic information about infection severity, risk of late reactivation, and response to therapy. Randomized trials, evaluating the need for antiviral therapy in kidney transplant recipients with asymptomatic infection and effective virus-specific T-cell immune response, are warranted.
背景
巨细胞病毒(CMV)疾病是移植后发病和死亡的主要原因。为了评估感染风险并监测对抗病毒治疗的反应,当前指南建议将病毒载量监测与CMV特异性免疫反应的直接评估相结合。我们使用酶联免疫斑点法(ELISpot)评估肾移植受者CMV病毒血症时的CMV特异性T细胞反应,并研究所获得的信息如何有助于管理CMV感染。
方法
对17例接受抢先抗病毒治疗且CMV定量聚合酶链反应(qPCR)≥500拷贝/毫升(移植后首次发作)的患者进行ELISpot评估,并分为弱反应者(9例基线ELISpot<25个斑点形成菌落[SFCs]/200,000外周血单个核细胞[PBMCs])和强反应者(8例基线ELISpot≥25 SFCs/200,000 PBMCs)。前瞻性记录随访1、2和24个月时两组之间的CMV特异性T细胞反应、感染严重程度、病毒载量和抗病毒治疗情况并进行比较。
结果
弱反应者和强反应者的人口统计学和移植特征相似。未观察到CMV疾病发作。与强反应者相比,弱反应者更易发生CMV综合征(56%对36.5%)和晚期病毒再激活(56%对25%)。弱反应者的基线病毒载量中位数更高(19,700对9265拷贝/毫升),且需要更长时间的抗病毒治疗(179对59.5天)。T细胞反应表现为两种主要模式:早期和延迟。
结论
ELISpot可提供有关感染严重程度、晚期再激活风险和治疗反应的预后信息。有必要进行随机试验,以评估无症状感染且病毒特异性T细胞免疫反应有效的肾移植受者对抗病毒治疗的需求。