Reduced antibody responses to vaccinations in children exposed to polychlorinated biphenyls.
Reduced antibody responses to vaccinations in children exposed to polychlorinated biphenyls.
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DOI：
10.1371/journal.pmed.0030311
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发表时间：
2006-08
期刊：
影响因子：
15.8
通讯作者：
Budtz-Jørgensen E
中科院分区：
文献类型：
--
作者：
Heilmann C;Grandjean P;Weihe P;Nielsen F;Budtz-Jørgensen E
发育时期接触多氯联苯 (PCB) 被认为是儿童免疫功能缺陷的可能原因。本研究旨在评估产前和产后接触 PCB 是否会影响儿童免疫接种的抗体反应。在法罗群岛形成了两个出生队列，那里的暴露情况差异很大，因为传统饮食可能包括受多氯联苯污染的鲸脂。产前暴露是根据孕妇血清和牛奶中 PCB 的浓度来确定的。在儿童期常规接种破伤风和白喉疫苗后，对 119 名儿童在 18 个月大时和 129 名儿童在 7 岁时进行了检查，并对他们的血清样本进行了破伤风和白喉类毒素抗体以及多氯联苯的分析。检查时累积 PCB 暴露量每增加一倍，18 个月时对白喉类毒素的抗体反应下降 24.4%（95% 置信区间 [CI]，1.63-41.9；p = 0.04）。 7 岁时白喉反应较低，并且与暴露无关。然而，破伤风类毒素抗体反应主要在 7 岁时受到影响，产前暴露量每增加一倍，就会降低 16.5%（95% CI，1.51-29.3；p = 0.03）。结构方程分析表明，产后早期暴露是疫苗接种反应下降的最重要预测因素。围产期接触多氯联苯的增加可能会对儿童疫苗接种的免疫反应产生不利影响。抗体产生不足的临床意义强调了预防免疫毒物暴露的必要性。对法罗群岛两个出生群体的研究表明，法罗群岛的饮食可能含有受多氯联苯 (PCB) 污染的鲸脂，接触 PCB 可能会降低儿童接种疫苗的免疫反应。如今，母亲们可能会担心儿童接种疫苗的潜在副作用，以及担心疫苗是否能完全保护孩子免受感染。但健康儿童的疫苗接种“效果”各不相同。例如，在接种破伤风和白喉疫苗后，一些儿童会产生大量抗体，保护他们免受这些严重的细菌性疾病的侵害。其他人的免疫反应较弱，有时甚至不充分。造成这种变异的原因尚不清楚，但一种可能是，一些婴儿正在发育的免疫系统因在出生前和出生后通过母乳接触多氯联苯 (PCB) 等“免疫毒物”而受到损害。这些稳定的人造化学品上世纪广泛用作电气设备中的绝缘体和阻燃剂，它们在环境中积聚并持续存在，影响动物和人类的健康。接触多氯联苯的婴儿通常胸腺（免疫系统细胞成熟的腺体）较小，产生的抗体数量减少，并且儿童感染的几率更高。鉴于这些观察结果，接触多氯联苯是否是儿童对疫苗接种产生不同免疫反应的部分原因？如果是这样，并且环境中的多氯联苯含量仍然很高，则可能有必要采取更密集的疫苗接种计划，以便所有儿童都得到充分的保护，免受传染病的侵害。在这项研究中，研究人员检查了产前和产后接触多氯联苯是否会影响儿童疫苗接种的抗体反应。研究人员招募了两组居住在北大西洋法罗群岛的儿童，一组出生于 1994-1995 年，另一组出生于 1999-2001 年。在这里，人们通过食用受污染的鲸脂而接触到高含量的多氯联苯。所有儿童都接受了白喉和破伤风的常规疫苗接种。引起这些疾病的细菌通过产生“类毒素”来实现这一点，因此注射无害量的这些有毒蛋白质来刺激保护性抗体反应。对于年龄较大的一组，他们在七岁半时采集了血液样本，以检测白喉和破伤风类毒素的抗体；对于较年轻的群体，在 18 个月大时采集了样本。儿童接触多氯联苯的情况是通过测量怀孕期间母亲血液中的多氯联苯、出生后不久母乳中的多氯联苯以及测试抗体时自己血液中的多氯联苯来评估的。研究人员发现，年轻儿童接触多氯联苯的总量每增加一倍，其对白喉类毒素的抗体反应就会减少近四分之一。较大儿童的破伤风类毒素反应因产前接触多氯联苯而减少了类似的量。尽管大多数儿童对这两种类毒素产生了足够的抗体来提供保护，但大约五分之一的年龄较大的儿童（主要是那些接触多氯联苯最高的儿童）的白喉类毒素抗体水平低得令人担忧。这些结果揭示了接触多氯联苯（尤其是出生后不久）与儿童接种疫苗后免疫保护作用降低之间的关联。然而，目前尚不清楚这种影响到底有多大。由于两个原因，这是不确定的。首先，对 PCB 接触量增加一倍会减少多少抗体反应的估计是不精确的——对于年幼的孩子来说，这种接触量的变化实际上可能对他们对白喉疫苗接种的反应影响很小，或者可能会使他们的反应减半。其次，多氯联苯暴露的估计仅基于三个体液样本，因此仅提供暴露的粗略指示。然而，这些对接触高浓度多氯联苯的儿童的结果表明，儿童的免疫功能也可能受到世界其他地方发现的较低水平多氯联苯的不利影响。研究人员写道，尽管免疫功能的变化很微妙，但它们可能具有重要的临床意义，并且可能会影响儿童的整体健康以及疫苗接种对传染病的预防程度。最后，这些研究结果表明，必须加大力度降低 PCB 暴露水平，以保护幼儿敏感的免疫系统免受这些强效免疫毒物的侵害。请通过此摘要的在线版本访问这些网站：http://dx.doi.org/10.1371/journal.pmed.0030311。 Tox Town 是美国国立卫生研究院的一个网站，提供有毒化学品和环境健康风险的介绍 美国有毒物质和疾病登记署有关 PCB 的情况说明书 美国环境保护署有关 PCB 的信息 MedlinePlus 百科全书有关免疫破伤风疫苗和白喉疫苗的条目 有关 PCB 和疫苗的维基百科页面（注：维基百科是免费在线版） 任何人都可以编辑的百科全书）
Developmental exposure to polychlorinated biphenyls (PCBs) has been implicated as a possible cause of deficient immune function in children. This study was designed to assess whether prenatal and postnatal exposure to PCBs impacts on antibody response to childhood immunizations. Two birth cohorts were formed in the Faroe Islands, where exposures vary widely, because traditional diets may include whale blubber contaminated with PCBs. Prenatal exposure was determined from maternal concentrations of PCBs in pregnancy serum and milk. Following routine childhood vaccinations against tetanus and diphtheria, 119 children were examined at 18 mo and 129 children at 7 y of age, and their serum samples were analyzed for tetanus and diphtheria toxoid antibodies and for PCBs. The antibody response to diphtheria toxoid decreased at age 18 mo by 24.4% (95% confidence interval [CI], 1.63–41.9; p = 0.04) for each doubling of the cumulative PCB exposure at the time of examination. The diphtheria response was lower at age 7 y and was not associated with the exposure. However, the tetanus toxoid antibody response was affected mainly at age 7 y, decreasing by 16.5% (95% CI, 1.51–29.3; p = 0.03) for each doubling of the prenatal exposure. Structural equation analysis showed that the early postnatal exposure was the most important predictor of a decreased vaccination response. Increased perinatal exposure to PCBs may adversely impact on immune responses to childhood vaccinations. The clinical implications of insufficient antibody production emphasize the need for prevention of immunotoxicant exposures. A study of two birth cohorts in the Faroe Islands, where diets may include whale blubber contaminated with polychlorinated biphenyls (PCBs), suggests exposure to PCBs may reduce immune response to childhood vaccinations. These days, mothers are as likely to worry about potential side-effects of childhood vaccinations as about whether they completely protect their child against infections. But healthy children vary in how well vaccinations “take.” After tetanus and diphtheria vaccination, for example, some children produce large quantities of antibodies that protect them against these serious bacterial diseases; others make a weaker, sometimes inadequate, immune response. What causes this variation is unclear, but one possibility is that the developing immune system is damaged in some babies by exposure both before birth and after birth through breast milk to “immunotoxicants” such as polychlorinated biphenyls (PCBs). These stable, man-made chemicals, which were widely used last century as insulators in electrical equipment and as fire retardants, accumulate and persist in the environment where they affect animal and human health. PCB-exposed babies often have a small thymus (the gland where immune system cells mature), make decreased amounts of antibodies, and have more childhood infections. Given these observations, could exposure to PCBs be partly responsible for the variable immunological responses of children to vaccination? If it is, and if environmental PCB levels remain high, it might be necessary to adapt more intensive vaccination programs so that all children are adequately protected against infectious diseases. In this study, the researchers examined whether prenatal and postnatal exposure to PCBs affects antibody responses to childhood vaccinations The researchers enrolled two groups of children—one group born in 1994–1995, the other in 1999–2001—living on the Faroe Islands in the North Atlantic. Here, people are exposed to high levels of PCBs through eating contaminated whale blubber. All the children received routine vaccinations against diphtheria and tetanus. The bacteria that cause these illnesses do so by producing a “toxoid,” so a harmless quantity of these toxic proteins is injected to stimulate a protective antibody response. For the older group, a blood sample was taken when they were seven and half years old to test for antibodies against diphtheria and tetanus toxoids; for the younger group, a sample was taken at 18 months. The exposure of the children to PCBs was assessed by measuring PCBs in their mothers' blood during pregnancy, in their mothers' milk soon after birth, and in their own blood when their antibodies were tested. The researchers found that the antibody response to diphtheria toxoid in the younger group of children was reduced by nearly a quarter for every doubling in their total exposure to PCBs. The tetanus toxoid response in the older children was reduced by a similar amount by prenatal exposure to PCBs. Although most of the children made enough antibodies to both toxoids to provide protection, about a fifth of the older children—mainly those with the highest exposures to PCBs—had worryingly low levels of diphtheria toxoid antibodies. These results reveal an association between exposure to PCBs, particularly soon after birth, and a reduction in immunoprotection after childhood vaccinations. It is not clear, however, exactly how big this effect may be. This is uncertain for two reasons. First, the estimates of how much antibody responses are reduced by doubling PCB exposure are imprecise—for the younger children this change in exposure might actually have very little effect on their response to diphtheria vaccination or it could halve their response. Second, the estimates of PCB exposures are based on only three samples of body fluids so provide only a crude indication of exposure. Nevertheless, these results in children exposed to high levels of PCBs indicate that the immune function of children might also be adversely affected by the lower levels of PCBs found elsewhere in the world. Although the changes in immune function are subtle, they could be clinically important, write the researchers, and might affect both the general health of children and the degree of protection against infectious diseases that vaccination provides. Finally, these findings suggest that efforts must be stepped up to reduce PCB exposure levels to protect the sensitive immune systems of young children from these potent immunotoxicants. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030311. Tox Town, a Web site available from the US National Institutes of Health, provides an introduction to toxic chemicals and environmental health risks US Agency for Toxic Substances and Disease Registry fact sheet on PCBs US Environmental Protection Agency information on PCBs MedlinePlus encyclopedia entries on immunization tetanus vaccine, and diphtheria vaccine Wikipedia pages on PCBs and vaccines (note: Wikipedia is a free online encyclopedia that anyone can edit)
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影响因子：
--
作者：
Gyhrs, A;Lyngholm, E;Heron, I
通讯作者：
Heron, I
影响因子：
5.1
作者：
Steuerwald, U;Weihe, P;Grandjean, P
通讯作者：
Grandjean, P
影响因子：
10.4
作者：
Weisglas-Kuperus, N;Patandin, S;Hooijkaas, H
通讯作者：
Hooijkaas, H
影响因子：
10.4
作者：
Longnecker, MP;Wolff, MS;Jensen, AA
通讯作者：
Jensen, AA
影响因子：
10.4
作者：
Dewailly, É;Ayotte, P;Roy, R
通讯作者：
Roy, R