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Sex differences in autoimmune disorders of the central nervous system

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Abstract

Stronger adaptive immune responses in females can be observed in different mammals, resulting in better control of infections compared to males. However, this presumably evolutionary difference likely also drives higher incidence of autoimmune diseases observed in humans. Here, we summarize sex differences in the most common autoimmune diseases of the central nervous system (CNS) and discuss recent advances in the understanding of possible underlying immunological and CNS intrinsic mechanisms. In multiple sclerosis (MS), the most common inflammatory disease of the CNS, but also in rarer conditions, such as neuromyelitis optica spectrum disorders (NMOSD) or neuronal autoantibody–mediated autoimmune encephalitis (AE), sex is one of the top risk factors, with women being more often affected than men. Immunological mechanisms driving the sex bias in autoimmune CNS diseases are complex and include hormonal as well as genetic and epigenetic effects, which could also be exerted indirectly via modulation of the microbiome. Furthermore, CNS intrinsic differences could underlie the sex bias in autoimmunity by differential responses to injury. The strong effects of sex on incidence and possibly also activity and progression of autoimmune CNS disorders suggest that treatments need to be tailored to each sex to optimize efficacy. To date, however, due to a lack of systematic studies on treatment responses in males versus females, evidence in this area is still sparse. We argue that studies taking sex differences into account could pave the way for sex-specific and therefore personalized treatment.

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Funding

This work has been funded by the Landesforschungsförderung Hamburg (LFF-FV 45) to M.A.F.

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Authors and Affiliations

  1. Institute of Neuroimmunology and Multiple Sclerosis (INIMS), Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg Eppendorf, Hamburg, Germany

    Stefan M. Gold, Anne Willing & Manuel A. Friese

  2. Department of Psychiatry, Charité - Universitätsmedizin Berlin, Cooperate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany

    Stefan M. Gold

  3. Department of Neurology, Christian-Albrechts-University Kiel, Kiel, Germany

    Frank Leypoldt

  4. Neuroimmunology Section, Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel/Lübeck, Kiel/Lübeck, Germany

    Frank Leypoldt

  5. NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany

    Friedemann Paul

  6. Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Berlin, Germany

    Friedemann Paul

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  1. Stefan M. Gold
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  5. Manuel A. Friese
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Correspondence to Manuel A. Friese.

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This article is a contribution to the special issue on Sex differences in immunity – Guest Editors: Hanna Lotter and Marcus Altfeld

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Gold, S.M., Willing, A., Leypoldt, F. et al. Sex differences in autoimmune disorders of the central nervous system. Semin Immunopathol 41, 177–188 (2019). https://doi.org/10.1007/s00281-018-0723-8

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