使用基于DNA甲基化的方法评估妇女健康倡议中绝经后妇女的免疫细胞图谱。

IF 5.7 2区 医学 Q1 Medicine Clinical Epigenetics Pub Date : 2023-04-28 DOI:10.1186/s13148-023-01488-8
Emily Nissen, Alexander Reiner, Simin Liu, Robert B Wallace, Annette M Molinaro, Lucas A Salas, Brock C Christensen, John K Wiencke, Devin C Koestler, Karl T Kelsey
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引用次数: 1

摘要

背景:在过去的十年里,基于DNA甲基化(DNAm)的去卷积方法已经被开发出来,该方法利用免疫细胞类型的细胞特异性DNAm标记物来提供对外周血中白细胞比例的准确估计。使用DNAm标记物的免疫细胞表型,称为免疫甲基组学或甲基化细胞术,提供了一种确定身体免疫细胞景观的解决方案,该解决方案不需要新鲜血液,并且可扩展到大样本量。尽管在基于DNAm的反褶积方面取得了重大进展,但对这些额外免疫层的临床和研究解释仍需要在人群水平上进行参考。在这里,我们的目的是为一组多民族绝经后美国妇女的免疫人群提供一些参考。结果:我们将基于DNAm的反褶积应用于妇女健康倡议中的大量绝经后妇女样本(基线,N = 58)或辅助的长寿命研究(WHI-LLS,N = 1237)以确定58个免疫参数的参考范围,包括19个白细胞亚群和20个衍生细胞比率的比例和绝对计数。参与者在抽血时年龄为50-94岁 = 898人(69.3%)自称为白人。使用线性回归模型,我们观察到抽血时的年龄与幼稚B、记忆CD4+、幼稚CD4+、天真CD8+、记忆CD8+记忆、中性粒细胞和自然杀伤细胞的绝对计数和比例之间存在显著关联。我们还评估了相隔14-18年在N = 52名参与者。我们的研究结果表明,在这段时间内,白细胞亚群的变化率具有较高的个体间变异性。而且,当进行配对t检验来测试基线访视和LLS访视之间的计数和比例差异时,幼稚B、记忆性CD4+、幼稚CD4+、天真CD8+、记忆性CD8+细胞和中性粒细胞发生了显著变化,与分析整个队列中与年龄的关联时的结果相似。结论:在这里,我们发现衍生细胞计数在很大程度上反映了与比例相关的免疫谱,并且这些新方法复制了与年龄相关的已知免疫谱。此外,我们证明了这种甲基化细胞术方法在流行病学研究中的潜在应用价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Assessment of immune cell profiles among post-menopausal women in the Women's Health Initiative using DNA methylation-based methods.

Background: Over the past decade, DNA methylation (DNAm)-based deconvolution methods that leverage cell-specific DNAm markers of immune cell types have been developed to provide accurate estimates of the proportions of leukocytes in peripheral blood. Immune cell phenotyping using DNAm markers, termed immunomethylomics or methylation cytometry, offers a solution for determining the body's immune cell landscape that does not require fresh blood and is scalable to large sample sizes. Despite significant advances in DNAm-based deconvolution, references at the population level are needed for clinical and research interpretation of these additional immune layers. Here we aim to provide some references for immune populations in a group of multi-ethnic post-menopausal American women.

Results: We applied DNAm-based deconvolution to a large sample of post-menopausal women enrolled in the Women's Health Initiative (baseline, N = 58) or the ancillary Long Life Study (WHI-LLS, N = 1237) to determine the reference ranges of 58 immune parameters, including proportions and absolute counts for 19 leukocyte subsets and 20 derived cell ratios. Participants were 50-94 years old at the time of blood draw, and N = 898 (69.3%) self-identified as White. Using linear regression models, we observed significant associations between age at blood draw and absolute counts and proportions of naïve B, memory CD4+, naïve CD4+, naïve CD8+, memory CD8+ memory, neutrophils, and natural killer cells. We also assessed the same immune profiles in a subset of paired longitudinal samples collected 14-18 years apart across N = 52 participants. Our results demonstrate high inter-individual variability in rates of change of leukocyte subsets over this time. And, when conducting paired t tests to test the difference in counts and proportions between the baseline visit and LLS visit, there were significant changes in naïve B, memory CD4+, naïve CD4+, naïve CD8+, memory CD8+ cells and neutrophils, similar to the results seen when analyzing the association with age in the entire cohort.

Conclusions: Here, we show that derived cell counts largely reflect the immune profile associated with proportions and that these novel methods replicate the known immune profiles associated with age. Further, we demonstrate the value this methylation cytometry approach can add as a potential application in epidemiological studies.

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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
期刊最新文献
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