Seminars in Immunopathology

, Volume 41, Issue 2, pp 177–188 | Cite as

Sex differences in autoimmune disorders of the central nervous system

  • Stefan M. Gold
  • Anne Willing
  • Frank Leypoldt
  • Friedemann Paul
  • Manuel A. FrieseEmail author


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.


Funding information

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


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Neuroimmunology and Multiple Sclerosis (INIMS), Center for Molecular Neurobiology Hamburg (ZMNH)University Medical Center Hamburg EppendorfHamburgGermany
  2. 2.Department of PsychiatryCharité - Universitätsmedizin Berlin, Cooperate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlinGermany
  3. 3.Department of NeurologyChristian-Albrechts-University KielKielGermany
  4. 4.Neuroimmunology Section, Institute of Clinical ChemistryUniversity Hospital Schleswig-Holstein Kiel/LübeckKiel/LübeckGermany
  5. 5.NeuroCure Clinical Research CenterCharité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlinGermany
  6. 6.Experimental and Clinical Research CenterMax Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin BerlinBerlinGermany

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