Jeeyoon Jennifer Ahn1, Julia O'Mahony2, Marina Moshkova3, Heather E Hanwell4, Hargurinder Singh3, Monan Angela Zhang1, Ruth Ann Marrie5, Amit Bar-Or6, Dessa A Sadovnick7, Shannon E Dunn8, Brenda L Banwell9. 1. Department of Immunology, University of Toronto, Toronto, ON, Canada. 2. Institute of Health Policy, Management and Evaluation, the University of Toronto/The Hospital for Sick Children, Toronto, ON, Canada. 3. Toronto General Research Institute, University Health Network, Toronto, ON, Canada. 4. Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada. 5. Departments of Internal Medicine and Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada. 6. Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. 7. Department of Medical Genetics and Division of Neurology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. 8. Department of Immunology, University of Toronto, Toronto, ON, Canada/Toronto General Research Institute, University Health Network, Toronto, ON, Canada/Women's College Research Institute, Toronto, ON, Canada sdunn@uhnresearch.ca. 9. Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.
Abstract
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.
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.
Authors: Anita L Belman; Lauren B Krupp; Cody S Olsen; John W Rose; Greg Aaen; Leslie Benson; Tanuja Chitnis; Mark Gorman; Jennifer Graves; Yolander Harris; Tim Lotze; Jayne Ness; Moses Rodriguez; Jan-Mendelt Tillema; Emmanuelle Waubant; Bianca Weinstock-Guttman; T Charles Casper Journal: Pediatrics Date: 2016-07 Impact factor: 7.124
Authors: Nina M de Gruijter; Meena Naja; Hannah Peckham; Anna Radziszewska; Matthew Kinsella; James Glenister; Elizabeth C Rosser; Gary E Butler; Elizabeth C Jury; Coziana Ciurtin Journal: Pediatr Rheumatol Online J Date: 2021-03-29 Impact factor: 3.054