CMV 特异性 CD8+ T 淋巴细胞产生的干扰素-γ 可提供针对危重症患者巨细胞病毒再激活的保护作用。
Interferon-γ production by CMV-specific CD8+ T lymphocytes provides protection against cytomegalovirus reactivation in critically ill patients.
机构信息
Unit of Infecious Diseases, Department of Internal Medicine, Hospital General Universitario, Universidad de Castilla La Mancha, Ciudad Real, Spain.
Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015), Madrid, Spain.
出版信息
Intensive Care Med. 2016 Jan;42(1):46-53. doi: 10.1007/s00134-015-4077-6. Epub 2015 Nov 4.
PURPOSE
To evaluate the usefulness of the secretion of interferon-γ (IFNγ) by cytomegalovirus (CMV)-specific CD8+ T cells to determine the risk of CMV reactivation in critically ill non-immunosuppressed patients.
METHODS
Two-center prospective cohort study including critically ill non-immunosuppressed CMV-seropositive patients admitted between December 2012 and March 2013. The incidence of CMV reactivation by polymerase chain reaction (real-time PCR) in plasma was investigated. IFNγ secretion by CMV-specific CD8+ T lymphocytes was determined at the time of admission to the intensive care unit (ICU) by means of the QuantiFERON(®)-CMV (QF-CMV) test. Cox regression analyses were performed to investigate CMV reactivation risk factors.
RESULTS
Fifty-three patients were included, of whom 13 (24.5%) presented CMV reactivation. Twenty-six patients (49.1%) were QF-CMV "reactive" (QF-CMV(R)). Of the 26 QF-CMV(R) patients, 11.5% (3/26) had CMV reactivation, whereas 37% (10/27) of QF-CMV "non reactive" patients (QF-CMV(NR)) presented reactivation (p = 0.03). By Cox regression, the presence of QF-CMV(R) at ICU admission (HR 0.09, 95% CI 0.02-0.44; p = 0.003) was associated with a decreased risk of CMV reactivation. The sensitivity, specificity, positive predictive value, and negative predictive value of QF-CMV were 77, 57, 37, and 88%, respectively. Eleven of the 53 patients (20.7%) died during the follow-up period. Mortality was more frequent in patients with CMV reactivation (6/13, 46.1 vs. 5/40, 12.5%; p = 0.015).
CONCLUSIONS
In critically ill non-immunosuppressed patients, the presence of functional CMV-specific CD8+ T lymphocyte response at intensive care unit admission provides protection against CMV reactivation.
目的
评估细胞巨化病毒（CMV）-特异性 CD8+T 细胞分泌干扰素-γ（IFNγ）对确定重症非免疫抑制患者 CMV 再激活风险的作用。
方法
纳入 2012 年 12 月至 2013 年 3 月间入住重症监护病房（ICU）的重症非免疫抑制 CMV 阳性患者进行前瞻性队列研究。通过聚合酶链反应（PCR）检测血浆中 CMV 再激活情况。通过 QuantiFERON（®）-CMV（QF-CMV）检测在 ICU 入院时测定 CMV 特异性 CD8+T 淋巴细胞 IFNγ的分泌情况。采用 Cox 回归分析探讨 CMV 再激活的危险因素。
结果
共纳入 53 例患者，其中 13 例（24.5%）出现 CMV 再激活。26 例（49.1%）患者 QF-CMV 检测呈“反应性”（QF-CMV（R））。在 26 例 QF-CMV（R）患者中，11.5%（3/26）出现 CMV 再激活，而 27 例 QF-CMV“非反应性”（QF-CMV（NR））患者中 37%（10/27）出现再激活（p=0.03）。Cox 回归分析显示，ICU 入院时 QF-CMV（R）的存在（HR 0.09，95%CI 0.02-0.44；p=0.003）与 CMV 再激活风险降低相关。QF-CMV 的敏感性、特异性、阳性预测值和阴性预测值分别为 77%、57%、37%和 88%。53 例患者中有 11 例（20.7%）在随访期间死亡。CMV 再激活患者的死亡率更高（6/13，46.1%比 5/40，12.5%；p=0.015）。
结论
在重症非免疫抑制患者中，ICU 入院时存在功能性 CMV 特异性 CD8+T 淋巴细胞反应可提供针对 CMV 再激活的保护。
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