The Increased Susceptibility of Women to Multiple Sclerosis

Duquette, Pierre; Pleines, J; Girard, Marc; Charest, Louise; Senécal-Quevillon, Micheline; Masse, Caroline

doi:10.1017/s0317167100041664

Cited by 149 publications

(47 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Females with MS outnumber males by approximately 2:1 37. Moreover, animal studies show that male mice, which are more resistant to EAE, produce more T H 2 cytokines than do female mice, whereas female mice, which are more susceptible, produce more T H 1 cytokines than do male mice 38.…”

Section: Resultsmentioning

confidence: 99%

Optic Neuritis in Different Strains of Mice by a Recombinant HSV-1 Expressing Murine Interleukin-2

Zandian

Belisle

Mott

et al. 2009

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose The authors have shown previously that a recombinant HSV-1 that constitutively expresses two copies of murine IL-2 (HSV-IL-2) induces demyelination by activated CD8+ T cells in the brain and spinal cord of ocularly infected female BALB/c mice. The present study was conducted to determine whether the ocular infection with this recombinant virus induces optic neuritis independent of virus dose, major histocompatibility complex (MHC) background, or sex. Methods Female BALB/c, C57BL/6, SJL/6, and 129SVE mice and male BALB/c mice were ocularly infected with different doses of recombinant HSV-IL-2 virus. Demyelination of optic nerves in infected mice was monitored histologically using Luxol fast blue staining and by measurement of visual-evoked cortical potentials (VECPs). Results Both focal and diffuse regions of demyelination of the optic nerves were observed in the HSV-IL-2–infected mice as early as day 10 after infection and as late as day 60 after infection (the final experimental time point) in all strains of mice tested. Optic nerve demyelination was not observed in control mice ocularly infected with HSV-IL-4 or wild-type HSV-1. VECP responses were delayed significantly in the HSV-IL-2–infected mice compared with mice infected with control viruses. Conclusions The results demonstrate for the first time that a combination of viral infection and constitutive expression of IL-2, but not IFN-γ or IL-4, can result in demyelination and visual impairment in the optic nerves of ocularly infected mice.

show abstract

Section: Resultsmentioning

confidence: 99%

Optic Neuritis in Different Strains of Mice by a Recombinant HSV-1 Expressing Murine Interleukin-2

Zandian

Belisle

Mott

et al. 2009

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…Notably, over the last decades, the sex ratio in MS appears to be increasing (see below). The difference in average age at onset between male and female patients is small but there is evidence that in younger patients (onset before age 20) the gender ratio is greater (3.2:1) than in the MS population as a whole (2:1) 4 .…”

Section: Gender Differences In Msmentioning

confidence: 95%

Sex-related factors in multiple sclerosis susceptibility and progression

2012

View full text Add to dashboard Cite

The pathogenesis of multiple sclerosis (MS) involves complex interactions between genetic susceptibility and environmental triggers. Clinical observations suggest that the study of sex differences may provide important insight into mechanisms of MS pathogenesis and progression. One clinical observation is that MS occurs more frequently in women than in men, indicating an impact of sex-related factors on susceptibility to MS. These factors include hormonal, genetic, and environmental influences, as well as gene x environment interactions and epigenetic mechanisms. Despite a higher incidence and more robust immune responses, females do not have a poorer prognosis, suggesting a biological mechanism of resilience. A second clinical observation is the pregnancy strongly affects disease activity, leading to a reduction in relapse rates in the last trimester but an increase post partum. However, pregnancy has little effects on long-term disability. Unraveling mechanisms underlying these clinical observations at the laboratory bench, with subsequent translation back to the bedside is a unique and potentially fruitful strategy in MS. In this paper, we review the current knowledge in the field and discuss novel therapeutic approaches currently in development that were derived from the study of sex-related factors.

show abstract

“…The etiology is unknown Paraparesis of the limbs, 'disturbances of the optic nerve', different neurological symptoms such as incontinence Relapsing/remitting or progressive disease course Polygenetic disease depending on both MHC and non-MHC genes [10] Genetically associated with HLA molecules [13,39] Autoreactive T cells recognize MBP epitopes [40] Perivascular lesions with infiltration of activated inflammatory cells such as T cells, macrophages and B cells Demyelination causes nerve death with subsequent paresis Female preponderance in disease onset, 10:1 compared with males [39] Disease phenotype of experimental autoimmune (allergic) encephalomyelitis (EAE) Can be induced in several species; mice, rats, guinea pigs, rabbits, apes and humans Can be induced with spinal cord homogenate (SCH), myelin proteins (MBP, PLP, MOG) or synthetic peptides thereof together with adjuvants FCA, and for some species pertussis toxin [41]. Polygenetic disease depending on both MHC and non-MHC genes [42] Development of acute or chronic relapsing paralytic disease, sometimes with disturbances of balance and incontinence [43] T cell-dependent disease [44] but B cells influence the disease course Inflammation caused demyelination, mostly by macrophages Shows a sex difference in SJL mice, with female development of chronic disease while male mice only show an acute disease course [45,46].…”

Section: Disease Phenotype Of Multiple Sclerosis (Ms)mentioning

confidence: 99%

Estrogen-mediated immunosuppression in autoimmune diseases

Jansson

Holmdahl

1998

Inflammation Research

156

View full text Add to dashboard Cite

Gender affects the susceptibility to many autoimmune diseases. Women have an increased risk of developing diseases such as rheumatoid arthritis and multiple sclerosis compared with men. The female preponderance is believed to depend in part on the influence of sex hormones on the immune system. The mechanism of estrogen-induced immune suppression both in human autoimmune diseases and their experimental animal model counterparts is discussed. In addition, the mechanisms of estrogen and anti-estrogens are discussed in relation to their possible use as future therapeutic anti-inflammatory agents.

show abstract

The Increased Susceptibility of Women to Multiple Sclerosis

Cited by 149 publications

References 57 publications

Optic Neuritis in Different Strains of Mice by a Recombinant HSV-1 Expressing Murine Interleukin-2

Optic Neuritis in Different Strains of Mice by a Recombinant HSV-1 Expressing Murine Interleukin-2

Sex-related factors in multiple sclerosis susceptibility and progression

Estrogen-mediated immunosuppression in autoimmune diseases

Contact Info

Product

Resources

About