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DETECTION OF CYTOMEGALOVIRUS DNA IN MONOCYTES CMV-SPECIFIC T CELLS AND IL-6 LEVELS IN OLDER ADULTS

机译:老年患者单核细胞CMV特异性T细胞和IL-6水平中巨细胞病毒DNA的检测

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摘要

Chronic cytomegalovirus (CMV) infection is believed to significantly contribute to T-cell immunosenescence and adverse health in older adults. A major barrier to advancement in this field has been that chronic CMV infection is diagnosed by anti-CMV IgG serology, a crude measure that merely indicates prior exposure to the virus and does not distinguish between past (resolved) or chronic (persistent) infections. We have optimized a nested PCR-based assay for qualitative detection of CMV DNA in the peripheral blood mononuclear cells (PBMCs). In this study, we evaluated 89 men and women InCHIANTI study participants (mean age=79, 65–96 years old). Among them, 36 were HLA-A2+ for whom CMV pp65-specific CD8+ T-cell frequencies were measured through class I tetramer analysis. The results showed that 56 of 89 participants (63%) had detectable monocytic CMV DNA while almost all (99%) were CMV seropositive. Those with detectable monocytic CMV DNA had significantly higher serum IL-6 levels than those without (1.81+1.5 vs 1.19+0.91 pg/ml, respectively, P=.01), regardless of anti-CMV IgG titers. Among 36 HLA-A2+ participants, those with detectable monocytic CMV DNA (n=20) had significantly higher CMV pp65-specific CD8+ T-cell frequency than those without (n=16, 3.65 ± 3.6% vs 0.86 ± 0.67%, respectively, P=.003). Taken together, these results suggest that detection of human CMV viral DNA in the PBMCs may be a better indicator than CMV seropositivity for increased IL-6 levels and CMV pp65-specific CD8+ T-cell expansion in older adults. Research is needed to further evaluate detection of monocytic CMV DNA as a valuable diagnostic tool of chronic CMV infection in older adults.
机译:人们认为,慢性巨细胞病毒(CMV)感染可显着促进老年人的T细胞免疫衰老和不良健康。该领域发展的主要障碍是通过抗CMV IgG血清学诊断出慢性CMV感染,这是一种粗略的衡量指标,仅表明以前曾接触过该病毒,不能区分过去(已解决)或慢性(持续)感染。我们已经优化了基于巢式PCR的检测方法,用于定性检测外周血单核细胞(PBMC)中的CMV DNA。在这项研究中,我们评估了89名InCHIANTI研究参与者(平均年龄= 79,65-96岁)。其中有36例是HLA-A2 +,通过I类四聚体分析测量了其CMV pp65特异性CD8 + T细胞频率。结果显示,在89名参与者中,有56名(63%)具有可检测的单核细胞巨细胞病毒DNA,而几乎所有(99%)均为CMV血清阳性。不论抗CMV IgG的效价如何,具有可检测的单核细胞巨细胞病毒DNA的患者血清IL-6水平均显着高于无血清的IL-6水平(分别为1.81 + 1.5对1.19 + 0.91 pg / ml,P = .01)。在36名HLA-A2 +参与者中,具有可检测的单核CMV DNA的参与者(n = 20)的CMV pp65特异性CD8 + T细胞频率显着高于没有参与者(n = 16,分别为3.65%±3.6%和0.86%±0.67%)。 P = .003)。综上所述,这些结果表明,在老年人中,增加的IL-6水平和CMV pp65特异性CD8 + T细胞扩增,在PBMC中检测人CMV病毒DNA可能比CMV血清阳性更好。需要进行研究以进一步评估单核细胞巨细胞病毒DNA的检测,将其作为老年人慢性巨细胞病毒感染的有价值的诊断工具。

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