Advertisement

Linking X to MS: Immunity and demyelination on the X-chromosome in MS

Published:September 21, 2022DOI:https://doi.org/10.1016/j.msard.2022.104190
      MS occurs 2-4 times more frequently in women than men (
      • Harbo H.F.
      • Gold R.
      • Tintore M.
      Sex and gender issues in multiple sclerosis.
      ,
      • Gbaguidi B.
      • Guillemin F.
      • Soudant M.
      • Debouverie M.
      • Mathey G.
      • Epstein J.
      Age-period-cohort analysis of the incidence of multiple sclerosis over twenty years in Lorraine, France.
      ), with some studies showing an increasing female-to-male ratio over time (
      • Trojano M.
      • Lucchese G.
      • Graziano G.
      • et al.
      Geographical variations in sex ratio trends over time in multiple sclerosis.
      ). Accordingly, abundant research focuses on the complex factors that may lead to this discrepancy. Hormonal influences (
      • Bove R.
      • Chitnis T.
      The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis.
      ) have been a prime focus, fueled by knowledge about the observed peak incidence in women during child-bearing years, the relative infrequency of relapses during pregnancy and rebound activity post-partum. The putative protective effects of testosterone vs. pro-inflammatory effects of estrogen have been elucidated in many studies (
      • Ysrraelit M.C.
      • Correale J.
      Impact of sex hormones on immune function and multiple sclerosis development.
      ). Furthermore, specific X-linked genetic factors that associate with this gap have long been under investigation and include the identification of a single SNP on the X chromosome (
      • International Multiple Sclerosis Genetics C
      Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility.
      ). But the question of whether X-linked immune- or myelin- related genes work together to produce an MS phenotype in women has not been answered yet.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Multiple Sclerosis and Related Disorders
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bjornevik K.
        • Cortese M.
        • Healy B.C.
        • et al.
        Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis.
        Science. 2022; 375: 296-301
        • Borziak K.
        • Finkelstein J.
        X-linked genetic risk factors that promote autoimmunity and dampen remyelination are associated with multiple sclerosis susceptibility.
        Mult. Scler. Relat. Disord. 2022; 66104065
        • Bove R.
        • Chitnis T.
        The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis.
        Mult. Scler. 2014; 20: 520-526
        • Bycroft C.
        • Freeman C.
        • Petkova D.
        • et al.
        The UK Biobank resource with deep phenotyping and genomic data.
        Nature. 2018; 562: 203-209
        • Gbaguidi B.
        • Guillemin F.
        • Soudant M.
        • Debouverie M.
        • Mathey G.
        • Epstein J.
        Age-period-cohort analysis of the incidence of multiple sclerosis over twenty years in Lorraine, France.
        Sci. Rep. 2022; 12: 1001
        • Harbo H.F.
        • Gold R.
        • Tintore M.
        Sex and gender issues in multiple sclerosis.
        Ther. Adv. Neurol. Disord. 2013; 6: 237-248
        • International Multiple Sclerosis Genetics C
        Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility.
        Science. 2019; 365
        • Johnson J.L.
        • Greaves L.
        • Repta R.
        Better science with sex and gender: facilitating the use of a sex and gender-based analysis in health research.
        Int. J. Equity Health. 2009; 8: 14
        • Palacios N.
        • Alonso A.
        • Bronnum-Hansen H.
        • Ascherio A.
        Smoking and increased risk of multiple sclerosis: parallel trends in the sex ratio reinforce the evidence.
        Ann. Epidemiol. 2011; 21: 536-542
        • Shams H.
        • Shao X.
        • Santaniello A.
        • et al.
        Polygenic risk score association with multiple sclerosis susceptibility and phenotype in Europeans.
        Brain. 2022; awac092https://doi.org/10.1093/brain/awac092
        • Trojano M.
        • Lucchese G.
        • Graziano G.
        • et al.
        Geographical variations in sex ratio trends over time in multiple sclerosis.
        PloS one. 2012; 7: e48078
        • Ysrraelit M.C.
        • Correale J.
        Impact of sex hormones on immune function and multiple sclerosis development.
        Immunology. 2019; 156: 9-22