Puberty in females enhances the risk of an outcome of multiple sclerosis in children and the development of central nervous system autoimmunity in mice

被引：37

作者：

Ahn, Jeeyoon Jennifer ^{[1
]}

O'Mahony, Julia ^{[2
,3
]}

Moshkova, Marina ^{[4
]}

Hanwell, Heather E. ^{[5
]}

Singh, Hargurinder ^{[4
]}

Zhang, Monan Angela ^{[1
]}

Marrie, Ruth Ann ^{[6
,7
]}

Bar-Or, Amit ^{[8
]}

Sadovnick, Dessa A. ^{[9
,10
]}

Dunn, Shannon E. ^{[1
,4
,11
]}

Banwell, Brenda L. ^{[12
]}

机构：

[1] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[2] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada

[3] Hosp Sick Children, Toronto, ON M5G 1X8, Canada

[4] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada

[5] Hosp Sick Children, Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada

[6] Univ Manitoba, Dept Internal Med, Winnipeg, MB, Canada

[7] Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB R3T 2N2, Canada

[8] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada

[9] Univ British Columbia, Fac Med, Dept Med Genet, Vancouver, BC, Canada

[10] Univ British Columbia, Fac Med, Div Neurol, Vancouver, BC, Canada

[11] Womens Coll Res Inst, Toronto, ON, Canada

[12] Univ Penn, Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA

来源：

MULTIPLE SCLEROSIS JOURNAL | 2015年 / 21卷 / 06期

基金：

加拿大健康研究院;

关键词：

Acquired demyelinating syndrome; antigen-presenting cells; autoimmune disease; central nervous system; experimental autoimmune encephalomyelitis; human study; mouse study; menarche; multiple sclerosis; puberty; risk factors; vitamin D; LUTEINIZING-HORMONE; DENDRITIC CELLS; AGE; ENCEPHALOMYELITIS; DEMYELINATION; MENARCHE; SUSCEPTIBILITY; MATURATION; ONSET;

D O I：

10.1177/1352458514551453

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Background: 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. Objective: To investigate the influence of female puberty on central nervous system (CNS) autoimmunity. Methods: 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. Results: 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. Conclusion: Puberty in females enhances CNS autoimmune mechanisms that lead to MS in humans and EAE in mice.

引用

页码：735 / 748

页数：14

共 36 条

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