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甲基汞和长链多不饱和脂肪酸与塞舌尔儿童发育研究中年轻人的免疫失调有关。

Methylmercury and long chain polyunsaturated fatty acids are associated with immune dysregulation in young adults from the Seychelles child development study.

机构信息

The Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom.

The School of Medicine and Dentistry, University of Rochester, NY, United States.

出版信息

Environ Res. 2020 Apr;183:109072. doi: 10.1016/j.envres.2019.109072. Epub 2020 Jan 7.

Abstract

BACKGROUND

Exposure to the environmental toxicant mercury (Hg) has been associated with immune dysregulation, including autoimmune disease, but few human studies have examined methylmercury (MeHg) exposure from fish consumption.

OBJECTIVES

We examined associations between MeHg exposure and biological markers of autoimmunity and inflammation while adjusting for long chain polyunsaturated fatty acids (LCPUFA).

METHOD

At age 19 years, hair total Hg (Y19Hg), LCPUFA status, a panel of 13 antinuclear antibodies (ANA), total serum immunoglobulins (Ig) IgG, IgA, and IgM and serum markers of inflammation (IL-1, IL-2, IL-6, IL-10, C-reactive protein (CRP), IFN-γ, TNF-α) were measured in the Seychelles Child Development Study (SCDS) Main Cohort (n = 497). Multivariable regression models investigated the association between Y19Hg and biomarkers, adjusting for prenatal total hair Hg (MatHg) and other relevant covariates, and with and without adjustment for LCPUFA.

RESULTS

With each 1 ppm increase in Y19Hg (mean 10.23 (SD 6.02) ppm) we observed a 4% increased odds in a positive Combined ANA following adjustment for the n6:n3 LCPUFA ratio (β = 0.036, 95%; CI: 0.001, 0.073). IgM was negatively associated with Y19Hg (β = -0.016, 95%CI: 0.016, -0.002) in models adjusted for n-3, n-6 LCPUFA and when separately adjusted for the n-6:n-3 LCPUFA ratio. No associations were observed with MatHg. Total n-3 LCPUFA status was associated with reduced odds of a positive anti-ribonuclear protein (RNP) A. The n-3 LCPUFA were negatively associated with IL-6, IL-10, CRP, IFN-γ, TNF-α and positively with TNF-α:IL-10. There were positive associations between the n-6:n-3 ratio and IL-6, IL-10, CRP, IFN-γ, TNF-α and a negative association with TNF-α:IL-10.

DISCUSSION

The Y19Hg exposure was associated with higher ANA and lower IgM albeit only following adjustment for the n-3 LCPUFA or the n-6:n-3 LCPUFA ratio. The clinical significance of these findings is unclear, but warrant follow up at an older age to determine any relationship to the onset of autoimmune disease.

摘要

背景

接触环境毒物汞(Hg)与免疫失调有关,包括自身免疫性疾病,但很少有人研究过鱼类消费导致的甲基汞(MeHg)暴露。

目的

我们研究了 MeHg 暴露与自身免疫和炎症的生物标志物之间的关联,同时调整了长链多不饱和脂肪酸(LCPUFA)的影响。

方法

在 19 岁时,塞舌尔儿童发展研究(SCDS)主要队列(n=497)中测量了头发总汞(Y19Hg)、LCPUFA 状况、一组 13 种抗核抗体(ANA)、总血清免疫球蛋白(IgG、IgA 和 IgM)以及血清炎症标志物(IL-1、IL-2、IL-6、IL-10、C-反应蛋白(CRP)、IFN-γ、TNF-α)。多变量回归模型研究了 Y19Hg 与生物标志物之间的关系,调整了产前总发汞(MatHg)和其他相关协变量,并在调整和不调整 LCPUFA 的情况下进行了调整。

结果

Y19Hg 每增加 1ppm(平均值 10.23(SD 6.02)ppm),在调整 n6:n3 LCPUFA 比值后,ANA 联合阳性的几率增加 4%(β=0.036,95%CI:0.001,0.073)。在调整 n-3、n-6 LCPUFA 以及单独调整 n-6:n-3 LCPUFA 比值的模型中,IgM 与 Y19Hg 呈负相关(β=-0.016,95%CI:0.016,-0.002)。MatHg 与这些结果无关。总 n-3 LCPUFA 状态与抗核糖核蛋白(RNP)A 阳性几率降低有关。n-3 LCPUFA 与 IL-6、IL-10、CRP、IFN-γ、TNF-α呈负相关,与 TNF-α:IL-10 呈正相关。n-6:n-3 比值与 IL-6、IL-10、CRP、IFN-γ、TNF-α呈正相关,与 TNF-α:IL-10 呈负相关。

讨论

Y19Hg 暴露与更高的 ANA 和更低的 IgM 相关,尽管仅在调整 n-3 LCPUFA 或 n-6:n-3 LCPUFA 比值后才如此。这些发现的临床意义尚不清楚,但需要在年龄较大时进行随访,以确定其与自身免疫性疾病发病之间的任何关系。

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