背景:肾移植后近期的良好效果主要归功于钙调磷酸酶抑制剂(CNI)的应用.但是机会性感染以及巨细胞病毒(CMV)感染则多发生于那些过度免疫抑制的患者。对于CNI的生物学效应的检测能够明确那些过度免疫抑制的肾移植患者,并对可能发生CMV感染的患者提供线索。方法:41名采用环孢素(n=18)或者他克莫司(n=23)的肾移植患者在移植后1个月内每周、11个月内每月抽取患者的全血用于监测全血抑制IL-2基因转录能力、患者细胞内T细胞对多克隆刺激后IL-2 、IFN-gamma和TNF-alpha的产生能力。结果:19名患者发生巨细胞病毒感染或者巨细胞病毒病,其余CMV血清类型D+R-以及D+R+显著相关(HR分别为19.6和6.6,P=0.0001)。免疫抑制治疗与患者T细胞所有细胞因子长期下降相关。但是,随访中任何一个时间点的检测可以预测其后CMV的发生。我们仅仅观察到CMV感染前1个星期累计TNF-alpha低水平产生的CD8+ T细胞的百分数和其后CMV的发生相关(小于1000单位的HR=1.39, P=0.04)。但是,该关系在调整CMV血清状态后不再显著。结论:该研究提示免疫监测对于诊断肾移植后过度免疫抑制抑制导致的CMV感染并不优于CNI的全血水平监测。
BACKGROUND: The short-term results of kidney transplantation are mainly attributed to the use of calcineurin inhibitors (CNI). However, opportunistic infections and cytomegalovirus (CMV) infections remain frequent and occur in the case of overimmunosuppression. Measurement of the biological effects of CNI could provide clues to identify overimmunosuppressed kidney transplant recipients (KTR) who would subsequently develop CMV infection. METHODS: Forty-one KTR given cyclosporine (n=18) or tacrolimus (n=23) were followed up every week during 1 month, then every month during 11 months, by measuring the patient's whole blood ability to inhibit interleukin-2 (IL-2) gene transcription and by measuring the patient's intracellular T-cell IL-2, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) production in response to polyclonal activation. RESULTS: Cytomegalovirus infection or disease occurred in 19 patients and was significantly associated with CMV serological status D+R- and D+R+ (HR=19.6 and 6.6, respectively, P=0.0001). Immunosuppressive treatment was associated with a long-lasting decrease of all cytokines produced by the patient's T-cells. However, none of these assays taken separately at any of the time points of the follow-up allowed to predict the occurrence of a subsequent CMV infection. We only observed a weak association between cumulative low levels of the percentage of TNF-alpha producing CD8+ T cells before CMV infection and its occurrence just afterwards (HR=1.39 for 1000 unit lower, P=0.04). However, this association did not remain significant after adjustment for CMV serological status. CONCLUSIONS: This study suggests that immunological monitoring is not better than CNI whole blood levels for diagnosis of overimmunosuppression-induced CMV infection in KTR. |