Anthony Bertrand, Jamie Sugrue, Tianai Lou, Nollaig M Bourke, Lluis Quintana-Murci, Violaine Saint-André, Cliona O'Farrelly, Darragh Duffy, the Milieu Intérieur Consortium
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引用次数: 0
Abstract
Individuals with low socioeconomic status (SES) are at greater risk of contracting and developing severe disease compared with people with higher SES. Age, sex, host genetics, smoking and cytomegalovirus (CMV) serostatus are known to have a major impact on human immune responses and thus susceptibility to infection. However, the impact of SES on immune variability is not well understood or explored. Here, we used data from the Milieu Intérieur project, a study of 1000 healthy volunteers with extensive demographic and biological data, to examine the effect of SES on immune variability. We developed an Elo-rating system using socioeconomic features such as education, income and home ownership status to objectively rank SES in the 1000 donors. We observed sex-specific SES associations, such as females with a low SES having a significantly higher frequency of CMV seropositivity compared with females with high SES, and males with a low SES having a significantly higher frequency of active smoking compared with males with a high SES. Using random forest models, we identified specific immune genes which were significantly associated with SES in both baseline and immune challenge conditions. Interestingly, many of the SES associations were sex stimuli specific, highlighting the complexity of these interactions. Our study provides a new way of computing SES in human populations that can help identify novel SES associations and reinforces biological evidence for SES-dependent susceptibility to infection. This should serve as a basis for further understanding the molecular mechanisms behind SES effects on immune responses and ultimately disease.
与社会经济地位较高的人相比,社会经济地位较低的人感染严重疾病的风险更大。众所周知,年龄、性别、宿主遗传学、吸烟和巨细胞病毒(CMV)血清状态对人体免疫反应有重大影响,因此对感染的易感性也有重大影响。然而,人们对社会经济地位对免疫变异性的影响还不甚了解,也没有进行深入探讨。在此,我们利用 "内部空间"(Milieu Intérieur)项目的数据,研究了 SES 对免疫变异性的影响。我们开发了一个 Elo 评级系统,利用教育、收入和房屋所有权状况等社会经济特征对 1000 名捐献者的 SES 进行客观排名。我们观察到了性别特异性的 SES 关联,例如与高 SES 女性相比,低 SES 女性的 CMV 血清阳性频率明显更高;与高 SES 男性相比,低 SES 男性的主动吸烟频率明显更高。利用随机森林模型,我们确定了在基线和免疫挑战条件下与社会经济地位显著相关的特定免疫基因。有趣的是,许多 SES 关联都具有性别刺激的特异性,这凸显了这些相互作用的复杂性。我们的研究提供了一种计算人类社会经济地位的新方法,有助于发现新的社会经济地位关联,并加强了社会经济地位依赖性感染易感性的生物学证据。这将为进一步了解社会经济地位对免疫反应和最终疾病的影响背后的分子机制奠定基础。
期刊介绍:
The Australasian Society for Immunology Incorporated (ASI) was created by the amalgamation in 1991 of the Australian Society for Immunology, formed in 1970, and the New Zealand Society for Immunology, formed in 1975. The aim of the Society is to encourage and support the discipline of immunology in the Australasian region. It is a broadly based Society, embracing clinical and experimental, cellular and molecular immunology in humans and animals. The Society provides a network for the exchange of information and for collaboration within Australia, New Zealand and overseas. ASI members have been prominent in advancing biological and medical research worldwide. We seek to encourage the study of immunology in Australia and New Zealand and are active in introducing young scientists to the discipline.