Department of Immunology, University of Toronto, Toronto, ON, Canada.
Institute of Health Policy, Management and Evaluation, the University of Toronto/The Hospital for Sick Children, Toronto, ON, Canada.
Mult Scler. 2015 May;21(6):735-48. doi: 10.1177/1352458514551453. Epub 2014 Dec 22.
For reasons that remain unclear, three times more women develop multiple sclerosis (MS) than men. This preponderance among women is evident only after 12 years of age, implicating pubertal factors in the risk of MS.
To investigate the influence of female puberty on central nervous system (CNS) autoimmunity.
We examined the relationship between age of menarche on MS outcomes in 116 female children (< 16 years old) whom presented with incident 'acquired demyelinating syndromes' (ADS) and were followed prospectively in the national Canadian Pediatric Demyelinating Disease Study, from 2004-2013. Furthermore, we directly investigated the effects of puberty on susceptibility to experimental autoimmune encephalomyelitis (EAE) in two groups of female mice that differed only in their pubertal status.
In the ADS children, a later age of menarche was associated with a decreased risk of subsequent MS diagnosis. This relationship persisted, after accounting for patient age at ADS presentation and the presence of ≥1 T2 lesions on brain magnetic resonance imaging (MRI), with a hazard ratio (HR) of 0.64; and additional factors that associate with MS outcomes in ADS children, including low vitamin D levels. Furthermore, we found female mice that had transitioned through puberty were more susceptible to EAE than age-matched, pre-pubertal mice.
Puberty in females enhances CNS autoimmune mechanisms that lead to MS in humans and EAE in mice.
原因尚不清楚，女性多发性硬化症（MS）的发病率是男性的三倍。这种女性优势仅在 12 岁后显现，提示青春期因素与 MS 风险有关。
研究女性青春期对中枢神经系统（CNS）自身免疫的影响。
我们在 2004 年至 2013 年期间，在全国加拿大儿科脱髓鞘疾病研究中，对 116 名女性儿童（<16 岁）前瞻性随访，这些儿童患有新发“获得性脱髓鞘综合征”（ADS），检查了初潮年龄与 MS 结局之间的关系。此外，我们直接研究了青春期对两组雌性小鼠易感性的影响，这两组小鼠仅在青春期状态上存在差异。
在 ADS 儿童中，初潮年龄较晚与随后 MS 诊断风险降低相关。这种关系在考虑到 ADS 表现时的患者年龄和脑磁共振成像（MRI）上存在≥1 个 T2 病变后仍然存在，风险比（HR）为 0.64；并且还有其他与 ADS 儿童 MS 结局相关的因素，包括低维生素 D 水平。此外，我们发现已经经历青春期的雌性小鼠比年龄匹配的未经历青春期的小鼠更容易发生 EAE。
女性青春期增强了中枢神经系统自身免疫机制，导致人类 MS 和小鼠 EAE。
