Ponsonby A-L, Dwyer T, van der Mei I, Kemp A, Blizzard L, Taylor B, Kilpatrick T, Simmons R
Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Australia.
Clin Exp Immunol. 2006 Dec;146(3):463-70. doi: 10.1111/j.1365-2249.2006.03235.x.
Higher sibling exposure is associated with a reduced risk of asthma and other T helper 2 (Th2)-type disorders, possibly through a beneficial effect of higher infection load. The effect on Th1 disorders such as multiple sclerosis (MS) is less clear. Here we examine the association between asthma and MS, taking into account early life sibling exposure. A population-based case-control study in Tasmania, Australia based on 136 cases of magnetic resonance imaging (MRI)-confirmed MS and 272 community controls, matched on sex and year of birth. Study measures include cumulative exposure to total, older or younger siblings by age 6 years, history of doctor-diagnosed asthma and serological IgG responses to herpes viruses. MS cases were more likely (P = 0.02) than controls to have asthma which began before age of onset of MS symptoms compared to the corresponding age for controls. The absence of younger sibling exposure by age 6 years potentiated (P = 0.04) the association between asthma and MS. Compared to those with younger sibling exposure and no asthma, the adjusted odds ratio for MS for those with asthma and no younger sibling exposure was 7.22 (95% CI: 2.52, 20.65). Early life sibling exposure was associated with altered IgG serological responses to Epstein-Barr virus (EBV) and herpes simplex virus 1 (HSV1) in adulthood. Reduced early life sibling exposure appeared to contribute to the excess of asthma among MS cases by the time of MS onset. MS development may reflect factors that relate to a general immuno-inflammatory up-regulation of immune activity as well as disease specific factors. The link between early life sibling exposure and the immune response to herpes group viral antigens is consistent with a protective role for early life infections.
较高的同胞暴露与哮喘及其他2型辅助性T细胞(Th2)相关疾病风险降低有关,这可能是由于较高感染负荷带来的有益影响。其对1型辅助性T细胞(Th1)相关疾病如多发性硬化症(MS)的影响尚不清楚。在此,我们考虑早期生活中的同胞暴露情况,研究哮喘与MS之间的关联。在澳大利亚塔斯马尼亚州开展了一项基于人群的病例对照研究,纳入136例经磁共振成像(MRI)确诊的MS患者及272名社区对照,根据性别和出生年份进行匹配。研究指标包括6岁前接触同胞总数、年长同胞或年幼同胞的累积暴露情况、医生诊断的哮喘病史以及对疱疹病毒的血清IgG反应。与对照组相应年龄相比,MS患者在MS症状出现前发病的哮喘发生率更高(P = 0.02)。6岁时无年幼同胞暴露会增强(P = 0.04)哮喘与MS之间的关联。与有年幼同胞暴露且无哮喘的人群相比,有哮喘且无年幼同胞暴露人群患MS的校正比值比为7.22(95%置信区间:2.52, 20.65)。早期生活中的同胞暴露与成年期对EB病毒(EBV)和单纯疱疹病毒1型(HSV1)的IgG血清学反应改变有关。MS发病时,早期生活中同胞暴露减少似乎导致了MS患者中哮喘过多。MS的发生可能反映了与免疫活性的一般免疫炎症上调相关的因素以及疾病特异性因素。早期生活中的同胞暴露与对疱疹病毒群病毒抗原的免疫反应之间的联系与早期生活感染的保护作用一致。