TY - JOUR
T1 - The increasing incidence and prevalence of female multiple sclerosis-A critical analysis of potential environmental factors
AU - Sellner, Johann
AU - Kraus, Jörg
AU - Awad, Amer
AU - Milo, Ron
AU - Hemmer, Bernhard
AU - Stüve, Olaf
PY - 2011/6
Y1 - 2011/6
N2 - Multiple sclerosis (MS) is the most common acquired inflammatory demyelinating disorder of the central nervous system (CNS). Not unlike many inflammatory diseases with a presumed autoimmune pathogenesis, it has been established that there is a female preponderance in prevalence. While in the past it was shown that there are two women for every man with a diagnosis of MS, recent serial cross-sectional assessments provide compelling evidence for an increase of the female to male sex ratio in patients with relapsing-remitting MS over the last decades. An understanding of this phenomenon might provide key insights into the pathogenesis of the disease but also may have implications for health-care strategies and further research efforts.We review possible etiologies for the gender disparity in MS, and we discuss possible underlying causes. We determined that the biologically most plausible explanations for a disproportional increase of MS among women in some population may be the role of vitamin D in MS pathogenesis. Decreased sun exposure may be a critical factor in diminished vitamin D levels in many recent cohort studies. Vitamin D insufficiency or deficiency has been shown to affect T cell differentiation and regulation, which may affect cellular immune responses against autoantigens and pathogens that have been associated with the etiology of MS. Vitamin D also appears to impact B cell activation and differentiation, another cell type that has been implicated in the inflammatory cascade underlying CNS autoimmune disease.
AB - Multiple sclerosis (MS) is the most common acquired inflammatory demyelinating disorder of the central nervous system (CNS). Not unlike many inflammatory diseases with a presumed autoimmune pathogenesis, it has been established that there is a female preponderance in prevalence. While in the past it was shown that there are two women for every man with a diagnosis of MS, recent serial cross-sectional assessments provide compelling evidence for an increase of the female to male sex ratio in patients with relapsing-remitting MS over the last decades. An understanding of this phenomenon might provide key insights into the pathogenesis of the disease but also may have implications for health-care strategies and further research efforts.We review possible etiologies for the gender disparity in MS, and we discuss possible underlying causes. We determined that the biologically most plausible explanations for a disproportional increase of MS among women in some population may be the role of vitamin D in MS pathogenesis. Decreased sun exposure may be a critical factor in diminished vitamin D levels in many recent cohort studies. Vitamin D insufficiency or deficiency has been shown to affect T cell differentiation and regulation, which may affect cellular immune responses against autoantigens and pathogens that have been associated with the etiology of MS. Vitamin D also appears to impact B cell activation and differentiation, another cell type that has been implicated in the inflammatory cascade underlying CNS autoimmune disease.
KW - Environmental trigger
KW - Female preponderance
KW - Multiple sclerosis
KW - Pathogenesis
KW - Sex ratio
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U2 - 10.1016/j.autrev.2011.02.006
DO - 10.1016/j.autrev.2011.02.006
M3 - Review article
C2 - 21354338
AN - SCOPUS:79957664940
SN - 1568-9972
VL - 10
SP - 495
EP - 502
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
IS - 8
ER -