Memory and Aging Center, Department of Neurology, University of California San Francisco, USA.
J Gerontol A Biol Sci Med Sci. 2021 Oct 13;76(11):1954-1961. doi: 10.1093/gerona/glab162.
Blood-based inflammatory markers hold considerable promise for diagnosis and prognostication of age-related neurodegenerative disease, though a paucity of research has empirically tested how reliably they can be measured across different experimental runs ("batches"). We quantified the interbatch reliability of 13 cytokines and chemokines in a cross-sectional study of 92 community-dwelling older adults (mean age = 74; 48% female). Plasma aliquots from the same blood draw were parallelly processed in 2 separate batches using the same analytic platform and procedures (high-performance electrochemiluminescence by Meso Scale Discovery). Interbatch correlations (Pearson's r) ranged from small and nonsignificant (r = .13 for macrophage inflammatory protein-1 alpha [MIP-1α]) to very large (r > .90 for interferon gamma [IFNγ], interleukin-10 [IL-10], interferon gamma-induced protein 10 [IP-10], MIP-1β, thymus and activation-regulated chemokine [TARC]) with most markers falling somewhere in between (.67 ≤ r ≤ .90 for IL-6, tumor necrosis factor alpha [TNF-α], Eotaxin, Eotaxin-3, monocyte chemoattractant protein-1 [MCP-1], MCP-4, macrophage-derived chemokine [MDC]). All markers, except for IL-6 and MCP-4, showed significant differences in absolute values between batches, with discrepancies ranging in effect size (Cohen's d) from small to moderate (0.2 ≤ |d| ≤ 0.5 for IL-10, IP-10, MDC) to large or very large (0.68 ≤ |d| ≤ 1.5 for IFNγ, TNF-α, Eotaxin, Eotaxin-3, MCP-1, MIP-1α, MIP-1β, TARC). Relatively consistent associations with external variables of interest (age, sex, systolic blood pressure, body mass index, cognition) were observed across batches. Taken together, our results suggest heterogeneity in measurement reliability of blood-based cytokines and chemokines, with some analytes outperforming others. Future work is needed to evaluate the generalizability of these findings while identifying potential sources of batch effect measurement error.
基于血液的炎症标志物在诊断和预测与年龄相关的神经退行性疾病方面具有很大的潜力,尽管很少有研究从实证角度测试它们在不同实验运行(“批次”)中可以多可靠地测量。我们在一项横断面研究中量化了 92 名居住在社区的老年人(平均年龄=74 岁;48%为女性)中 13 种细胞因子和趋化因子的批间可靠性。使用相同的分析平台和程序(Meso Scale Discovery 的高性能电化学发光),从同一份血液样本中平行处理血浆等分试样。批间相关性(Pearson r)范围从很小且无统计学意义(巨噬细胞炎性蛋白-1α[MIP-1α]的 r =.13)到非常大(干扰素γ[IFNγ]、白细胞介素-10[IL-10]、干扰素γ诱导蛋白 10[IP-10]、MIP-1β、胸腺激活调节趋化因子[TARC]的 r >.90),大多数标志物介于两者之间(IL-6、肿瘤坏死因子-α[TNF-α]、嗜酸性粒细胞趋化因子[Eotaxin]、Eotaxin-3、单核细胞趋化蛋白-1[MCP-1]、MCP-4、巨噬细胞衍生趋化因子[MDC]的 r =.67 ≤.90)。除了 IL-6 和 MCP-4 之外,所有标志物在批次之间的绝对值都存在显著差异,差异的效应大小(Cohen's d)从小到大(IL-10、IP-10、MDC 的 |d| ≤ 0.5)到中到大(IFNγ、TNF-α、Eotaxin、Eotaxin-3、MCP-1、MIP-1α、MIP-1β、TARC 的 |d| ≥ 0.68)。在不同批次中,与感兴趣的外部变量(年龄、性别、收缩压、体重指数、认知)相对一致的相关性。综合来看,我们的结果表明,基于血液的细胞因子和趋化因子的测量可靠性存在异质性,其中一些分析物的表现优于其他分析物。需要进一步的工作来评估这些发现的普遍性,同时确定批次效应测量误差的潜在来源。