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羊水趋化因子与自闭症谱系障碍:利用丹麦历史性出生队列进行的探索性研究。

Amniotic fluid chemokines and autism spectrum disorders: an exploratory study utilizing a Danish Historic Birth Cohort.

机构信息

Department of Epidemiology, Aarhus University School of Public Health, Aarhus, Denmark.

出版信息

Brain Behav Immun. 2012 Jan;26(1):170-6. doi: 10.1016/j.bbi.2011.09.003. Epub 2011 Sep 10.

Abstract

INTRODUCTION

Elevated levels of chemokines have been reported in plasma and brain tissue of individuals with Autism Spectrum Disorders (ASD). The aim of this study was to examine chemokine levels in amniotic fluid (AF) samples of individuals diagnosed with ASD and their controls.

MATERIAL AND METHODS

A Danish Historic Birth Cohort (HBC) kept at Statens Serum Institute, Copenhagen was utilized. Using data from Danish nation-wide health registers, a case-control study design of 414 cases and 820 controls was adopted. Levels of MCP-1, MIP-1α and RANTES were analyzed using Luminex xMAP technology. Case-control differences were assessed as dichotomized at below the 10th percentile or above the 90th percentile cut-off points derived from the control biomarker distributions (logistic regression) or continuous measures (tobit regression).

RESULTS AND CONCLUSION

AF volume for 331 cases and 698 controls was sufficient for Luminex analysis. Including all individuals in the cohort yielded no significant differences in chemokine levels in cases versus controls. Logistic regression analyses, performed on individuals diagnosed using ICD-10 only, showed increased risk for ASD with elevated MCP-1 (elevated 90th percentile adjusted OR: 2.32 [95% CI: 1.17-4.61]) compared to controls. An increased risk for infantile autism with elevated MCP-1 was also found (adjusted OR: 2.28 [95% CI: 1.16-4.48]). Elevated levels of MCP-1 may decipher an etiologic immunologic dysfunction or play rather an indirect role in the pathophysiology of ASD. Further studies to confirm its role and to identify the potential pathways through which MCP-1 may contribute to the development of ASD are necessary.

摘要

简介

在自闭症谱系障碍(ASD)患者的血浆和脑组织中已报道趋化因子水平升高。本研究旨在检查诊断为 ASD 的个体的羊水(AF)样本中的趋化因子水平及其对照。

材料和方法

利用哥本哈根 Statens Serum Institute 的丹麦历史出生队列(HBC)。使用来自丹麦全国健康登记处的数据,采用 414 例病例和 820 例对照的病例对照研究设计。使用 Luminex xMAP 技术分析 MCP-1、MIP-1α 和 RANTES 水平。使用来自控制生物标志物分布的第 10 百分位数以下或第 90 百分位数以上的截断点(逻辑回归)或连续测量(Tobit 回归)将病例对照差异作为二分类进行评估。

结果和结论

331 例和 698 例的 AF 量足以进行 Luminex 分析。在队列中的所有个体中,病例与对照之间的趋化因子水平没有差异。仅使用 ICD-10 诊断的个体进行的逻辑回归分析显示,MCP-1 升高与 ASD 的风险增加相关(升高的 90 百分位调整 OR:2.32 [95% CI:1.17-4.61])与对照组相比。还发现 MCP-1 升高与婴儿自闭症的风险增加相关(调整后的 OR:2.28 [95% CI:1.16-4.48])。MCP-1 水平升高可能表明病因免疫功能障碍或在 ASD 的病理生理学中起间接作用。需要进一步的研究来确认其作用,并确定 MCP-1 可能通过哪些潜在途径有助于 ASD 的发展。

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