Skip to main content

Advertisement

Log in

Sex differences in autoimmune disorders of the central nervous system

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Ngo ST, Steyn FJ, McCombe PA (2014) Gender differences in autoimmune disease. Front Neuroendocrinol 35(3):347–369. https://doi.org/10.1016/j.yfrne.2014.04.004

    Article  CAS  PubMed  Google Scholar 

  2. Klein SL, Flanagan KL (2016) Sex differences in immune responses. Nat Rev Immunol 16(10):626–638. https://doi.org/10.1038/nri.2016.90

    Article  CAS  PubMed  Google Scholar 

  3. Dendrou CA, Fugger L, Friese MA (2015) Immunopathology of multiple sclerosis. Nat Rev Immunol 15(9):545–558. https://doi.org/10.1038/nri3871

    Article  CAS  PubMed  Google Scholar 

  4. Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O (2018) Multiple sclerosis. Lancet 391(10130):1622–1636. https://doi.org/10.1016/S0140-6736(18)30481-1

    Article  PubMed  Google Scholar 

  5. Orton SM, Herrera BM, Yee IM, Valdar W, Ramagopalan SV, Sadovnick AD, Ebers GC, Canadian Collaborative Study G (2006) Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol 5(11):932–936. https://doi.org/10.1016/S1474-4422(06)70581-6

    Article  PubMed  Google Scholar 

  6. Tremlett H, Zhao Y, Devonshire V, Neurologists UBC (2009) Natural history comparisons of primary and secondary progressive multiple sclerosis reveals differences and similarities. J Neurol 256(3):374–381. https://doi.org/10.1007/s00415-009-0039-7

    Article  PubMed  Google Scholar 

  7. Dunn SE, Lee H, Pavri FR, Zhang MA (2015) Sex-based differences in multiple sclerosis (part I): biology of disease incidence. Curr Top Behav Neurosci 26:29–56. https://doi.org/10.1007/7854_2015_371

    Article  CAS  PubMed  Google Scholar 

  8. Ramagopalan SV, Valdar W, Criscuoli M, DeLuca GC, Dyment DA, Orton SM, Yee IM, Ebers GC, Sadovnick AD, Canadian Collaborative Study G (2009) Age of puberty and the risk of multiple sclerosis: a population based study. Eur J Neurol 16(3):342–347. https://doi.org/10.1111/j.1468-1331.2008.02431.x

    Article  CAS  PubMed  Google Scholar 

  9. Koch-Henriksen N, Sorensen PS (2010) The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol 9(5):520–532. https://doi.org/10.1016/S1474-4422(10)70064-8

    Article  PubMed  Google Scholar 

  10. Koch-Henriksen N, Thygesen LC, Stenager E, Laursen B, Magyari M (2018) Incidence of MS has increased markedly over six decades in Denmark particularly with late onset and in women. Neurology 90(22):e1954–e1963. https://doi.org/10.1212/WNL.0000000000005612

    Article  PubMed  Google Scholar 

  11. Trojano M, Lucchese G, Graziano G, Taylor BV, Simpson S Jr, Lepore V, Grand’maison F, Duquette P, Izquierdo G, Grammond P, Amato MP, Bergamaschi R, Giuliani G, Boz C, Hupperts R, Van Pesch V, Lechner-Scott J, Cristiano E, Fiol M, Oreja-Guevara C, Saladino ML, Verheul F, Slee M, Paolicelli D, Tortorella C, D’Onghia M, Iaffaldano P, Direnzo V, Butzkueven H, Group MSS, the New Zealand MSPSG (2012) Geographical variations in sex ratio trends over time in multiple sclerosis. PLoS One 7(10):e48078. https://doi.org/10.1371/journal.pone.0048078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rotstein DL, Chen H, Wilton AS, Kwong JC, Marrie RA, Gozdyra P, Krysko KM, Kopp A, Copes R, Tu K (2018) Temporal trends in multiple sclerosis prevalence and incidence in a large population. Neurology 90(16):e1435–e1441. https://doi.org/10.1212/WNL.0000000000005331

    Article  PubMed  Google Scholar 

  13. Kalincik T, Vivek V, Jokubaitis V, Lechner-Scott J, Trojano M, Izquierdo G, Lugaresi A, Grand’maison F, Hupperts R, Oreja-Guevara C, Bergamaschi R, Iuliano G, Alroughani R, Van Pesch V, Amato MP, Slee M, Verheul F, Fernandez-Bolanos R, Fiol M, Spitaleri DL, Cristiano E, Gray O, Cabrera-Gomez JA, Shaygannejad V, Herbert J, Vucic S, Needham M, Petkovska-Boskova T, Sirbu CA, Duquette P, Girard M, Grammond P, Boz C, Giuliani G, Rio ME, Barnett M, Flechter S, Moore F, Singhal B, Bacile EA, Saladino ML, Shaw C, Skromne E, Poehlau D, Vella N, Spelman T, Liew D, Kilpatrick TJ, Butzkueven H, Group MSS (2013) Sex as a determinant of relapse incidence and progressive course of multiple sclerosis. Brain 136(Pt 12):3609–3617. https://doi.org/10.1093/brain/awt281

    Article  PubMed  Google Scholar 

  14. Pozzilli C, Tomassini V, Marinelli F, Paolillo A, Gasperini C, Bastianello S (2003) ‘Gender gap’ in multiple sclerosis: magnetic resonance imaging evidence. Eur J Neurol 10(1):95–97

    Article  CAS  PubMed  Google Scholar 

  15. Weatherby SJ, Mann CL, Davies MB, Fryer AA, Haq N, Strange RC, Hawkins CP (2000) A pilot study of the relationship between gadolinium-enhancing lesions, gender effect and polymorphisms of antioxidant enzymes in multiple sclerosis. J Neurol 247(6):467–470

    Article  CAS  PubMed  Google Scholar 

  16. Stone LA, Smith ME, Albert PS, Bash CN, Maloni H, Frank JA, McFarland HF (1995) Blood-brain barrier disruption on contrast-enhanced MRI in patients with mild relapsing-remitting multiple sclerosis: relationship to course, gender, and age. Neurology 45(6):1122–1126

    Article  CAS  PubMed  Google Scholar 

  17. Barkhof F, Held U, Simon JH, Daumer M, Fazekas F, Filippi M, Frank JA, Kappos L, Li D, Menzler S, Miller DH, Petkau J, Wolinsky J, Sylvia Lawry Centre for MSR (2005) Predicting gadolinium enhancement status in MS patients eligible for randomized clinical trials. Neurology 65(9):1447–1454. https://doi.org/10.1212/01.wnl.0000183149.87975.32

    Article  CAS  PubMed  Google Scholar 

  18. Antulov R, Weinstock-Guttman B, Cox JL, Hussein S, Durfee J, Caiola C, Dwyer MG, Bergsland N, Abdelrahman N, Stosic M, Hojnacki D, Munschauer FE, Miletic D, Zivadinov R (2009) Gender-related differences in MS: a study of conventional and nonconventional MRI measures. Mult Scler 15(3):345–354. https://doi.org/10.1177/1352458508099479

    Article  CAS  PubMed  Google Scholar 

  19. Libert C, Dejager L, Pinheiro I (2010) The X chromosome in immune functions: when a chromosome makes the difference. Nat Rev Immunol 10(8):594–604. https://doi.org/10.1038/nri2815

    Article  CAS  PubMed  Google Scholar 

  20. Kantarci OH, Hebrink DD, Schaefer-Klein J, Sun Y, Achenbach S, Atkinson EJ, Heggarty S, Cotleur AC, de Andrade M, Vandenbroeck K, Pelfrey CM, Weinshenker BG (2008) Interferon gamma allelic variants: sex-biased multiple sclerosis susceptibility and gene expression. Arch Neurol 65(3):349–357. https://doi.org/10.1001/archneurol.2007.66

    Article  PubMed  Google Scholar 

  21. Moldovan IR, Cotleur AC, Zamor N, Butler RS, Pelfrey CM (2008) Multiple sclerosis patients show sexual dimorphism in cytokine responses to myelin antigens. J Neuroimmunol 193(1–2):161–169. https://doi.org/10.1016/j.jneuroim.2007.10.010

    Article  CAS  PubMed  Google Scholar 

  22. Pelfrey CM, Cotleur AC, Lee JC, Rudick RA (2002) Sex differences in cytokine responses to myelin peptides in multiple sclerosis. J Neuroimmunol 130(1–2):211–223

    Article  CAS  PubMed  Google Scholar 

  23. Runmarker B, Andersson C, Oden A, Andersen O (1994) Prediction of outcome in multiple sclerosis based on multivariate models. J Neurol 241(10):597–604

    Article  CAS  PubMed  Google Scholar 

  24. Confavreux C, Vukusic S, Adeleine P (2003) Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain 126(Pt 4):770–782

    Article  PubMed  Google Scholar 

  25. Savettieri G, Messina D, Andreoli V, Bonavita S, Caltagirone C, Cittadella R, Farina D, Fazio MC, Girlanda P, Le Pira F, Liguori M, Lugaresi A, Nocentini U, Reggio A, Salemi G, Tedeschi G, Trojano M, Valentino P, Quattrone A (2004) Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis. J Neurol 251(10):1208–1214. https://doi.org/10.1007/s00415-004-0508-y

    Article  PubMed  Google Scholar 

  26. Weinshenker BG (1994) Natural history of multiple sclerosis. Ann Neurol 36(Suppl):S6–S11

    Article  PubMed  Google Scholar 

  27. Weinshenker BG, Rice GP, Noseworthy JH, Carriere W, Baskerville J, Ebers GC (1991) The natural history of multiple sclerosis: a geographically based study. 3. Multivariate analysis of predictive factors and models of outcome. Brain 114(Pt 2):1045–1056

    Article  PubMed  Google Scholar 

  28. Tomassini V, Pozzilli C (2009) Sex hormones, brain damage and clinical course of multiple sclerosis. J Neurol Sci 286(1–2):35–39. https://doi.org/10.1016/j.jns.2009.04.014

    Article  CAS  PubMed  Google Scholar 

  29. Shirani A, Zhao Y, Kingwell E, Rieckmann P, Tremlett H (2012) Temporal trends of disability progression in multiple sclerosis: findings from British Columbia, Canada (1975–2009). Mult Scler 18(4):442–450. https://doi.org/10.1177/1352458511422097

    Article  PubMed  Google Scholar 

  30. Koch M, Kingwell E, Rieckmann P, Tremlett H, Neurologists UMC (2010) The natural history of secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 81(9):1039–1043. https://doi.org/10.1136/jnnp.2010.208173

    Article  PubMed  Google Scholar 

  31. Ribbons KA, McElduff P, Boz C, Trojano M, Izquierdo G, Duquette P, Girard M, Grand’Maison F, Hupperts R, Grammond P, Oreja-Guevara C, Petersen T, Bergamaschi R, Giuliani G, Barnett M, van Pesch V, Amato MP, Iuliano G, Fiol M, Slee M, Verheul F, Cristiano E, Fernandez-Bolanos R, Saladino ML, Rio ME, Cabrera-Gomez J, Butzkueven H, van Munster E, Den Braber-Moerland L, La Spitaleri D, Lugaresi A, Shaygannejad V, Gray O, Deri N, Alroughani R, Lechner-Scott J (2015) Male sex is independently associated with faster disability accumulation in relapse-onset MS but not in primary progressive MS. PLoS One 10(6):e0122686. https://doi.org/10.1371/journal.pone.0122686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Beatty WW, Aupperle RL (2002) Sex differences in cognitive impairment in multiple sclerosis. Clin Neuropsychol 16(4):472–480. https://doi.org/10.1076/clin.16.4.472.13904

    Article  PubMed  Google Scholar 

  33. Schoonheim MM, Popescu V, Rueda Lopes FC, Wiebenga OT, Vrenken H, Douw L, Polman CH, Geurts JJ, Barkhof F (2012) Subcortical atrophy and cognition: sex effects in multiple sclerosis. Neurology 79(17):1754–1761. https://doi.org/10.1212/WNL.0b013e3182703f46

    Article  PubMed  Google Scholar 

  34. Kremer L, Mealy M, Jacob A, Nakashima I, Cabre P, Bigi S, Paul F, Jarius S, Aktas O, Elsone L, Mutch K, Levy M, Takai Y, Collongues N, Banwell B, Fujihara K, de Seze J (2014) Brainstem manifestations in neuromyelitis optica: a multicenter study of 258 patients. Mult Scler 20(7):843–847. https://doi.org/10.1177/1352458513507822

    Article  CAS  PubMed  Google Scholar 

  35. Schmidt F, Zimmermann H, Mikolajczak J, Oertel FC, Pache F, Weinhold M, Schinzel J, Bellmann-Strobl J, Ruprecht K, Paul F, Brandt AU (2017) Severe structural and functional visual system damage leads to profound loss of vision-related quality of life in patients with neuromyelitis optica spectrum disorders. Mult Scler Relat Disord 11:45–50. https://doi.org/10.1016/j.msard.2016.11.008

    Article  PubMed  Google Scholar 

  36. Mori M, Kuwabara S, Paul F (2018) Worldwide prevalence of neuromyelitis optica spectrum disorders. J Neurol Neurosurg Psychiatry 89(6):555–556. https://doi.org/10.1136/jnnp-2017-317566

    Article  PubMed  Google Scholar 

  37. Finke C, Zimmermann H, Pache F, Oertel FC, Chavarro VS, Kramarenko Y, Bellmann-Strobl J, Ruprecht K, Brandt AU, Paul F (2018) Association of visual impairment in neuromyelitis optica spectrum disorder with visual network reorganization. JAMA Neurol 75(3):296–303. https://doi.org/10.1001/jamaneurol.2017.3890

    Article  PubMed  PubMed Central  Google Scholar 

  38. Asseyer S, Schmidt F, Chien C, Scheel M, Ruprecht K, Bellmann-Strobl J, Brandt AU, Paul F (2018) Pain in AQP4-IgG-positive and MOG-IgG-positive neuromyelitis optica spectrum disorders. Mult Scler J Exp Transl Clin 4(3):2055217318796684. https://doi.org/10.1177/2055217318796684

    Article  PubMed  PubMed Central  Google Scholar 

  39. Oertel FC, Kuchling J, Zimmermann H, Chien C, Schmidt F, Knier B, Bellmann-Strobl J, Korn T, Scheel M, Klistorner A, Ruprecht K, Paul F, Brandt AU (2017) Microstructural visual system changes in AQP4-antibody-seropositive NMOSD. Neurol Neuroimmunol Neuroinflamm 4(3):e334. https://doi.org/10.1212/NXI.0000000000000334

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chavarro VS, Mealy MA, Simpson A, Lacheta A, Pache F, Ruprecht K, Gold SM, Paul F, Brandt AU, Levy M (2016) Insufficient treatment of severe depression in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm 3(6):e286. https://doi.org/10.1212/NXI.0000000000000286

    Article  PubMed  PubMed Central  Google Scholar 

  41. Penner IK, Paul F (2017) Fatigue as a symptom or comorbidity of neurological diseases. Nat Rev Neurol 13(11):662–675. https://doi.org/10.1038/nrneurol.2017.117

    Article  PubMed  Google Scholar 

  42. Mealy MA, Kessler RA, Rimler Z, Reid A, Totonis L, Cutter G, Kister I, Levy M (2018) Mortality in neuromyelitis optica is strongly associated with African ancestry. Neurol Neuroimmunol Neuroinflamm 5(4):e468. https://doi.org/10.1212/NXI.0000000000000468

    Article  PubMed  PubMed Central  Google Scholar 

  43. Zekeridou A, Lennon VA (2015) Aquaporin-4 autoimmunity. Neurol Neuroimmunol Neuroinflamm 2(4):e110. https://doi.org/10.1212/NXI.0000000000000110

    Article  PubMed  PubMed Central  Google Scholar 

  44. Metz I, Beissbarth T, Ellenberger D, Pache F, Stork L, Ringelstein M, Aktas O, Jarius S, Wildemann B, Dihazi H, Friede T, Bruck W, Ruprecht K, Paul F (2016) Serum peptide reactivities may distinguish neuromyelitis optica subgroups and multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 3(2):e204. https://doi.org/10.1212/NXI.0000000000000204

    Article  PubMed  PubMed Central  Google Scholar 

  45. Takeshita Y, Obermeier B, Cotleur AC, Spampinato SF, Shimizu F, Yamamoto E, Sano Y, Kryzer TJ, Lennon VA, Kanda T, Ransohoff RM (2017) Effects of neuromyelitis optica-IgG at the blood-brain barrier in vitro. Neurol Neuroimmunol Neuroinflamm 4(1):e311. https://doi.org/10.1212/NXI.0000000000000311

    Article  PubMed  Google Scholar 

  46. Waters P, Reindl M, Saiz A, Schanda K, Tuller F, Kral V, Nytrova P, Sobek O, Nielsen HH, Barington T, Lillevang ST, Illes Z, Rentzsch K, Berthele A, Berki T, Granieri L, Bertolotto A, Giometto B, Zuliani L, Hamann D, van Pelt ED, Hintzen R, Hoftberger R, Costa C, Comabella M, Montalban X, Tintore M, Siva A, Altintas A, Deniz G, Woodhall M, Palace J, Paul F, Hartung HP, Aktas O, Jarius S, Wildemann B, Vedeler C, Ruiz A, Leite MI, Trillenberg P, Probst M, Saschenbrecker S, Vincent A, Marignier R (2016) Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica. J Neurol Neurosurg Psychiatry 87(9):1005–1015. https://doi.org/10.1136/jnnp-2015-312601

    Article  PubMed  Google Scholar 

  47. Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, Kleiter I, Kleinschnitz C, Berthele A, Brettschneider J, Hellwig K, Hemmer B, Linker RA, Lauda F, Mayer CA, Tumani H, Melms A, Trebst C, Stangel M, Marziniak M, Hoffmann F, Schippling S, Faiss JH, Neuhaus O, Ettrich B, Zentner C, Guthke K, Hofstadt-van Oy U, Reuss R, Pellkofer H, Ziemann U, Kern P, Wandinger KP, Bergh FT, Boettcher T, Langel S, Liebetrau M, Rommer PS, Niehaus S, Munch C, Winkelmann A, Zettl UU, Metz I, Veauthier C, Sieb JP, Wilke C, Hartung HP, Aktas O, Paul F (2012) Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation 9:14. https://doi.org/10.1186/1742-2094-9-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Borisow N, Kleiter I, Gahlen A, Fischer K, Wernecke KD, Pache F, Ruprecht K, Havla J, Krumbholz M, Kumpfel T, Aktas O, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Weissert R, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker RA, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Winkelmann A, Marouf W, Ruckriem L, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C, Hellwig K, Nemos (2017) Influence of female sex and fertile age on neuromyelitis optica spectrum disorders. Mult Scler 23(8):1092–1103. https://doi.org/10.1177/1352458516671203

    Article  PubMed  Google Scholar 

  49. Siritho S, Apiwattanakul M, Nakashima I, Takahashi T, Fujihara K, Prayoonwiwat N (2014) Features of anti-aquaporin 4 antibody-seronegative Thai patients with neuromyelitis optica spectrum disorders: a comparison with seropositive cases. J Neurol Sci 341(1–2):17–21. https://doi.org/10.1016/j.jns.2014.03.033

    Article  CAS  PubMed  Google Scholar 

  50. Pandit L, Asgari N, Apiwattanakul M, Palace J, Paul F, Leite MI, Kleiter I, Chitnis T, Consortium GIC, Biorepository for Neuromyelitis O (2015) Demographic and clinical features of neuromyelitis optica: a review. Mult Scler 21(7):845–853. https://doi.org/10.1177/1352458515572406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG, International Panel for NMOD (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85(2):177–189. https://doi.org/10.1212/WNL.0000000000001729

    Article  PubMed  PubMed Central  Google Scholar 

  52. Hyun JW, Jeong IH, Joung A, Kim SH, Kim HJ (2016) Evaluation of the 2015 diagnostic criteria for neuromyelitis optica spectrum disorder. Neurology 86(19):1772–1779. https://doi.org/10.1212/WNL.0000000000002655

    Article  PubMed  Google Scholar 

  53. Bove R, Elsone L, Alvarez E, Borisow N, Cortez MM, Mateen FJ, Mealy MA, Mutch K, Tobyne S, Ruprecht K, Buckle G, Levy M, Wingerchuk DM, Paul F, Cross AH, Weinshenker B, Jacob A, Klawiter EC, Chitnis T (2017) Female hormonal exposures and neuromyelitis optica symptom onset in a multicenter study. Neurol Neuroimmunol Neuroinflamm 4(3):e339. https://doi.org/10.1212/NXI.0000000000000339

    Article  PubMed  PubMed Central  Google Scholar 

  54. Kitley J, Leite MI, Nakashima I, Waters P, McNeillis B, Brown R, Takai Y, Takahashi T, Misu T, Elsone L, Woodhall M, George J, Boggild M, Vincent A, Jacob A, Fujihara K, Palace J (2012) Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain 135(Pt 6):1834–1849. https://doi.org/10.1093/brain/aws109

    Article  PubMed  Google Scholar 

  55. Jarius S, Ruprecht K, Kleiter I, Borisow N, Asgari N, Pitarokoili K, Pache F, Stich O, Beume LA, Hummert MW, Trebst C, Ringelstein M, Aktas O, Winkelmann A, Buttmann M, Schwarz A, Zimmermann H, Brandt AU, Franciotta D, Capobianco M, Kuchling J, Haas J, Korporal-Kuhnke M, Lillevang ST, Fechner K, Schanda K, Paul F, Wildemann B, Reindl M, in cooperation with the Neuromyelitis Optica Study G (2016) MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflamm 13(1):279. https://doi.org/10.1186/s12974-016-0717-1

    Article  CAS  Google Scholar 

  56. Sepulveda M, Armangue T, Sola-Valls N, Arrambide G, Meca-Lallana JE, Oreja-Guevara C, Mendibe M, Alvarez de Arcaya A, Aladro Y, Casanova B, Olascoaga J, Jimenez-Huete A, Fernandez-Fournier M, Ramio-Torrenta L, Cobo-Calvo A, Vinals M, de Andres C, Meca-Lallana V, Cervello A, Calles C, Rubio MB, Ramo-Tello C, Caminero A, Munteis E, Antiguedad AR, Blanco Y, Villoslada P, Montalban X, Graus F, Saiz A (2016) Neuromyelitis optica spectrum disorders: comparison according to the phenotype and serostatus. Neurol Neuroimmunol Neuroinflamm 3(3):e225. https://doi.org/10.1212/NXI.0000000000000225

    Article  PubMed  PubMed Central  Google Scholar 

  57. Kim SM, Woodhall MR, Kim JS, Kim SJ, Park KS, Vincent A, Lee KW, Waters P (2015) Antibodies to MOG in adults with inflammatory demyelinating disease of the CNS. Neurol Neuroimmunol Neuroinflamm 2(6):e163. https://doi.org/10.1212/NXI.0000000000000163

    Article  PubMed  PubMed Central  Google Scholar 

  58. Waters P, Woodhall M, O’Connor KC, Reindl M, Lang B, Sato DK, Jurynczyk M, Tackley G, Rocha J, Takahashi T, Misu T, Nakashima I, Palace J, Fujihara K, Leite MI, Vincent A (2015) MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol Neuroimmunol Neuroinflamm 2(3):e89. https://doi.org/10.1212/NXI.0000000000000089

    Article  PubMed  PubMed Central  Google Scholar 

  59. Narayan R, Simpson A, Fritsche K, Salama S, Pardo S, Mealy M, Paul F, Levy M (2018) MOG antibody disease: a review of MOG antibody seropositive neuromyelitis optica spectrum disorder. Mult Scler Relat Disord 25:66–72. https://doi.org/10.1016/j.msard.2018.07.025

    Article  PubMed  Google Scholar 

  60. Jarius S, Paul F, Aktas O, Asgari N, Dale RC, de Seze J, Franciotta D, Fujihara K, Jacob A, Kim HJ, Kleiter I, Kumpfel T, Levy M, Palace J, Ruprecht K, Saiz A, Trebst C, Weinshenker BG, Wildemann B (2018) MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J Neuroinflammation 15(1):134. https://doi.org/10.1186/s12974-018-1144-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Spadaro M, Gerdes LA, Krumbholz M, Ertl-Wagner B, Thaler FS, Schuh E, Metz I, Blaschek A, Dick A, Bruck W, Hohlfeld R, Meinl E, Kumpfel T (2016) Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 3(5):e257. https://doi.org/10.1212/NXI.0000000000000257

    Article  PubMed  PubMed Central  Google Scholar 

  62. Jarius S, Kleiter I, Ruprecht K, Asgari N, Pitarokoili K, Borisow N, Hummert MW, Trebst C, Pache F, Winkelmann A, Beume LA, Ringelstein M, Stich O, Aktas O, Korporal-Kuhnke M, Schwarz A, Lukas C, Haas J, Fechner K, Buttmann M, Bellmann-Strobl J, Zimmermann H, Brandt AU, Franciotta D, Schanda K, Paul F, Reindl M, Wildemann B, in cooperation with the Neuromyelitis Optica Study G (2016) MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: brainstem involvement - frequency, presentation and outcome. J Neuroinflamm 13(1):281. https://doi.org/10.1186/s12974-016-0719-z

    Article  CAS  Google Scholar 

  63. Hamid SHM, Whittam D, Saviour M, Alorainy A, Mutch K, Linaker S, Solomon T, Bhojak M, Woodhall M, Waters P, Appleton R, Duddy M, Jacob A (2018) Seizures and encephalitis in myelin oligodendrocyte glycoprotein IgG disease vs aquaporin 4 IgG disease. JAMA Neurol 75(1):65–71. https://doi.org/10.1001/jamaneurol.2017.3196

    Article  PubMed  Google Scholar 

  64. Ogawa R, Nakashima I, Takahashi T, Kaneko K, Akaishi T, Takai Y, Sato DK, Nishiyama S, Misu T, Kuroda H, Aoki M, Fujihara K (2017) MOG antibody-positive, benign, unilateral, cerebral cortical encephalitis with epilepsy. Neurol Neuroimmunol Neuroinflamm 4(2):e322. https://doi.org/10.1212/NXI.0000000000000322

    Article  PubMed  PubMed Central  Google Scholar 

  65. Pandit L, Mustafa S, Uppoor R, Nakashima I, Takahashi T, Kaneko K (2018) Reversible paraspinal muscle hyperintensity in anti-MOG antibody-associated transverse myelitis. Neurol Neuroimmunol Neuroinflamm 5(1):e412. https://doi.org/10.1212/NXI.0000000000000412

    Article  PubMed  Google Scholar 

  66. Ramanathan S, Mohammad S, Tantsis E, Nguyen TK, Merheb V, Fung VSC, White OB, Broadley S, Lechner-Scott J, Vucic S, Henderson APD, Barnett MH, Reddel SW, Brilot F, Dale RC, Australasian, New Zealand MOGSG (2018) Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry 89(2):127–137. https://doi.org/10.1136/jnnp-2017-316880

    Article  PubMed  Google Scholar 

  67. Hyun JW, Woodhall MR, Kim SH, Jeong IH, Kong B, Kim G, Kim Y, Park MS, Irani SR, Waters P, Kim HJ (2017) Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases. J Neurol Neurosurg Psychiatry 88(10):811–817. https://doi.org/10.1136/jnnp-2017-315998

    Article  PubMed  Google Scholar 

  68. Jurynczyk M, Tackley G, Kong Y, Geraldes R, Matthews L, Woodhall M, Waters P, Kuker W, Craner M, Weir A, DeLuca GC, Kremer S, Leite MI, Vincent A, Jacob A, de Seze J, Palace J (2017) Brain lesion distribution criteria distinguish MS from AQP4-antibody NMOSD and MOG-antibody disease. J Neurol Neurosurg Psychiatry 88(2):132–136. https://doi.org/10.1136/jnnp-2016-314005

    Article  PubMed  Google Scholar 

  69. Cobo-Calvo A, Ruiz A, Maillart E, Audoin B, Zephir H, Bourre B, Ciron J, Collongues N, Brassat D, Cotton F, Papeix C, Durand-Dubief F, Laplaud D, Deschamps R, Cohen M, Biotti D, Ayrignac X, Tilikete C, Thouvenot E, Brochet B, Dulau C, Moreau T, Tourbah A, Lebranchu P, Michel L, Lebrun-Frenay C, Montcuquet A, Mathey G, Debouverie M, Pelletier J, Labauge P, Derache N, Coustans M, Rollot F, De Seze J, Vukusic S, Marignier R, Ofsep, Group NS (2018) Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study. Neurology 90(21):e1858–e1869. https://doi.org/10.1212/WNL.0000000000005560

    Article  CAS  PubMed  Google Scholar 

  70. Siritho S, Sato DK, Kaneko K, Fujihara K, Prayoonwiwat N (2016) The clinical spectrum associated with myelin oligodendrocyte glycoprotein antibodies (anti-MOG-Ab) in Thai patients. Mult Scler 22(7):964–968. https://doi.org/10.1177/1352458515614093

    Article  CAS  PubMed  Google Scholar 

  71. Sato DK, Callegaro D, Lana-Peixoto MA, Waters PJ, de Haidar Jorge FM, Takahashi T, Nakashima I, Apostolos-Pereira SL, Talim N, Simm RF, Lino AM, Misu T, Leite MI, Aoki M, Fujihara K (2014) Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 82(6):474–481. https://doi.org/10.1212/WNL.0000000000000101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Zamvil SS, Slavin AJ (2015) Does MOG Ig-positive AQP4-seronegative opticospinal inflammatory disease justify a diagnosis of NMO spectrum disorder? Neurol Neuroimmunol Neuroinflamm 2(1):e62. https://doi.org/10.1212/NXI.0000000000000062

    Article  PubMed  PubMed Central  Google Scholar 

  73. Reindl M, Rostasy K (2015) MOG antibody-associated diseases. Neurol Neuroimmunol Neuroinflamm 2(1):e60. https://doi.org/10.1212/NXI.0000000000000060

    Article  PubMed  PubMed Central  Google Scholar 

  74. Dos Passos GR, Oliveira LM, da Costa BK, Apostolos-Pereira SL, Callegaro D, Fujihara K, Sato DK (2018) MOG-IgG-associated optic neuritis, encephalitis, and myelitis: lessons learned from neuromyelitis optica spectrum disorder. Front Neurol 9:217. https://doi.org/10.3389/fneur.2018.00217

    Article  PubMed  PubMed Central  Google Scholar 

  75. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Hoftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Pruss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostasy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15(4):391–404. https://doi.org/10.1016/S1474-4422(15)00401-9

    Article  PubMed  PubMed Central  Google Scholar 

  76. Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA (2012) The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California encephalitis project. Clin Infect Dis 54(7):899–904. https://doi.org/10.1093/cid/cir1038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Vora NM, Holman RC, Mehal JM, Steiner CA, Blanton J, Sejvar J (2014) Burden of encephalitis-associated hospitalizations in the United States, 1998–2010. Neurology 82(5):443–451. https://doi.org/10.1212/WNL.0000000000000086

    Article  PubMed  Google Scholar 

  78. Dalmau J, Graus F (2018) Antibody-mediated encephalitis. N Engl J Med 378(9):840–851. https://doi.org/10.1056/NEJMra1708712

    Article  PubMed  Google Scholar 

  79. Dalmau J (2016) NMDA receptor encephalitis and other antibody-mediated disorders of the synapse: the 2016 Cotzias lecture. Neurology 87(23):2471–2482. https://doi.org/10.1212/WNL.0000000000003414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 12(2):157–165. https://doi.org/10.1016/S1474-4422(12)70310-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Zalel Y, Piura B, Elchalal U, Czernobilsky B, Antebi S, Dgani R (1996) Diagnosis and management of malignant germ cell ovarian tumors in young females. Int J Gynaecol Obstet 55(1):1–10

    Article  CAS  PubMed  Google Scholar 

  82. Thompson J, Bi M, Murchison AG, Makuch M, Bien CG, Chu K, Farooque P, Gelfand JM, Geschwind MD, Hirsch LJ, Somerville E, Lang B, Vincent A, Leite MI, Waters P, Irani SR, Faciobrachial Dystonic Seizures Study G (2018) The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain 141(2):348–356. https://doi.org/10.1093/brain/awx323

    Article  PubMed  Google Scholar 

  83. Arino H, Armangue T, Petit-Pedrol M, Sabater L, Martinez-Hernandez E, Hara M, Lancaster E, Saiz A, Dalmau J, Graus F (2016) Anti-LGI1-associated cognitive impairment: presentation and long-term outcome. Neurology 87(8):759–765. https://doi.org/10.1212/WNL.0000000000003009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. van Sonderen A, Arino H, Petit-Pedrol M, Leypoldt F, Kortvelyessy P, Wandinger KP, Lancaster E, Wirtz PW, Schreurs MW, Sillevis Smitt PA, Graus F, Dalmau J, Titulaer MJ (2016) The clinical spectrum of Caspr2 antibody-associated disease. Neurology 87(5):521–528. https://doi.org/10.1212/WNL.0000000000002917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Mueller SH, Farber A, Pruss H, Melzer N, Golombeck KS, Kumpfel T, Thaler F, Elisak M, Lewerenz J, Kaufmann M, Suhs KW, Ringelstein M, Kellinghaus C, Bien CG, Kraft A, Zettl UK, Ehrlich S, Handreka R, Rostasy K, Then Bergh F, Faiss JH, Lieb W, Franke A, Kuhlenbaumer G, Wandinger KP, Leypoldt F, German Network for Research on Autoimmune E (2018) Genetic predisposition in anti-LGI1 and anti-NMDA receptor encephalitis. Ann Neurol 83(4):863–869. https://doi.org/10.1002/ana.25216

    Article  CAS  PubMed  Google Scholar 

  86. Binks S, Varley J, Lee W, Makuch M, Elliott K, Gelfand JM, Jacob S, Leite MI, Maddison P, Chen M, Geschwind MD, Grant E, Sen A, Waters P, McCormack M, Cavalleri GL, Barnardo M, Knight JC, Irani SR (2018) Distinct HLA associations of LGI1 and CASPR2-antibody diseases. Brain. https://doi.org/10.1093/brain/awy109

  87. Gresa-Arribas N, Arino H, Martinez-Hernandez E, Petit-Pedrol M, Sabater L, Saiz A, Dalmau J, Graus F (2015) Antibodies to inhibitory synaptic proteins in neurological syndromes associated with glutamic acid decarboxylase autoimmunity. PLoS One 10(3):e0121364. https://doi.org/10.1371/journal.pone.0121364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Malter MP, Helmstaedter C, Urbach H, Vincent A, Bien CG (2010) Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol 67(4):470–478. https://doi.org/10.1002/ana.21917

    Article  PubMed  Google Scholar 

  89. Ramien C, Taenzer A, Lupu A, Heckmann N, Engler JB, Patas K, Friese MA, Gold SM (2016) Sex effects on inflammatory and neurodegenerative processes in multiple sclerosis. Neurosci Biobehav Rev 67:137–146. https://doi.org/10.1016/j.neubiorev.2015.12.015

    Article  CAS  PubMed  Google Scholar 

  90. Kim RY, Mangu D, Hoffman AS, Kavosh R, Jung E, Itoh N, Voskuhl R (2018) Oestrogen receptor and beta; ligand acts on CD11c and plus; cells to mediate protection in experimental autoimmune encephalomyelitis. Brain 141(1):132–147. https://doi.org/10.1093/brain/awx315

    Article  PubMed  Google Scholar 

  91. Pakpoor J, Wotton CJ, Schmierer K, Giovannoni G, Goldacre MJ (2016) Gender identity disorders and multiple sclerosis risk: a national record-linkage study. Mult Scler 22(13):1759–1762. https://doi.org/10.1177/1352458515627205

    Article  PubMed  Google Scholar 

  92. Russi AE, Ebel ME, Yang Y, Brown MA (2018) Male-specific IL-33 expression regulates sex-dimorphic EAE susceptibility. Proc Natl Acad Sci U S A 115(7):E1520–E1529. https://doi.org/10.1073/pnas.1710401115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Massa MG, David C, Jorg S, Berg J, Gisevius B, Hirschberg S, Linker RA, Gold R, Haghikia A (2017) Testosterone differentially affects T cells and neurons in murine and human models of Neuroinflammation and neurodegeneration. Am J Pathol 187(7):1613–1622. https://doi.org/10.1016/j.ajpath.2017.03.006

    Article  CAS  PubMed  Google Scholar 

  94. Org E, Mehrabian M, Parks BW, Shipkova P, Liu X, Drake TA, Lusis AJ (2016) Sex differences and hormonal effects on gut microbiota composition in mice. Gut Microbes 7(4):313–322. https://doi.org/10.1080/19490976.2016.1203502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Yurkovetskiy L, Burrows M, Khan AA, Graham L, Volchkov P, Becker L, Antonopoulos D, Umesaki Y, Chervonsky AV (2013) Gender bias in autoimmunity is influenced by microbiota. Immunity 39(2):400–412. https://doi.org/10.1016/j.immuni.2013.08.013

    Article  CAS  PubMed  Google Scholar 

  96. van den Hoogen WJ, Laman JD, Hart BA (2017) Modulation of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis by food and gut microbiota. Front Immunol 8:1081. https://doi.org/10.3389/fimmu.2017.01081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Haase S, Haghikia A, Wilck N, Muller DN, Linker RA (2018) Impacts of microbiome metabolites on immune regulation and autoimmunity. Immunology 154(2):230–238. https://doi.org/10.1111/imm.12933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Benedek G, Zhang J, Nguyen H, Kent G, Seifert HA, Davin S, Stauffer P, Vandenbark AA, Karstens L, Asquith M, Offner H (2017) Estrogen protection against EAE modulates the microbiota and mucosal-associated regulatory cells. J Neuroimmunol 310:51–59. https://doi.org/10.1016/j.jneuroim.2017.06.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Qu K, Zaba LC, Giresi PG, Li R, Longmire M, Kim YH, Greenleaf WJ, Chang HY (2015) Individuality and variation of personal regulomes in primary human T cells. Cell Syst 1(1):51–61. https://doi.org/10.1016/j.cels.2015.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Souyris M, Cenac C, Azar P, Daviaud D, Canivet A, Grunenwald S, Pienkowski C, Chaumeil J, Mejia JE, Guery JC (2018) TLR7 escapes X chromosome inactivation in immune cells. Sci Immunol 3(19). https://doi.org/10.1126/sciimmunol.aap8855

  101. Voskuhl RR, Sawalha AH, Itoh Y (2018) Sex chromosome contributions to sex differences in multiple sclerosis susceptibility and progression. Mult Scler 24(1):22–31. https://doi.org/10.1177/1352458517737394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Du S, Itoh N, Askarinam S, Hill H, Arnold AP, Voskuhl RR (2014) XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 111(7):2806–2811. https://doi.org/10.1073/pnas.1307091111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Moore S, Patel R, Hannsun G, Yang J, Tiwari-Woodruff SK (2013) Sex chromosome complement influences functional callosal myelination. Neuroscience 245:166–178. https://doi.org/10.1016/j.neuroscience.2013.04.017

    Article  CAS  PubMed  Google Scholar 

  104. Li R, Sun X, Shu Y, Mao Z, Xiao L, Qiu W, Lu Z, Hu X (2017) Sex differences in outcomes of disease-modifying treatments for multiple sclerosis: a systematic review. Mult Scler Relat Disord 12:23–28. https://doi.org/10.1016/j.msard.2017.01.001

    Article  PubMed  Google Scholar 

  105. Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, Borisow N, Kleiter I, Aktas O, Kumpfel T, Neuromyelitis Optica Study G (2014) Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol 261(1):1–16. https://doi.org/10.1007/s00415-013-7169-7

    Article  CAS  PubMed  Google Scholar 

  106. Ellwardt E, Ellwardt L, Bittner S, Zipp F (2018) Monitoring B-cell repopulation after depletion therapy in neurologic patients. Neurol Neuroimmunol Neuroinflamm 5(4):e463. https://doi.org/10.1212/NXI.0000000000000463

    Article  PubMed  PubMed Central  Google Scholar 

  107. Das G, Damotte V, Gelfand JM, Bevan C, Cree BAC, Do L, Green AJ, Hauser SL, Bove R (2018) Rituximab before and during pregnancy: a systematic review, and a case series in MS and NMOSD. Neurol Neuroimmunol Neuroinflamm 5(3):e453. https://doi.org/10.1212/NXI.0000000000000453

    Article  PubMed  PubMed Central  Google Scholar 

  108. Gahlen A, Trampe AK, Haupeltshofer S, Ringelstein M, Aktas O, Berthele A, Wildemann B, Gold R, Jarius S, Kleiter I (2017) Aquaporin-4 antibodies in patients treated with natalizumab for suspected MS. Neurol Neuroimmunol Neuroinflamm 4(4):e363. https://doi.org/10.1212/NXI.0000000000000363

    Article  PubMed  PubMed Central  Google Scholar 

  109. Gelfand JM, Cotter J, Klingman J, Huang EJ, Cree BA (2014) Massive CNS monocytic infiltration at autopsy in an alemtuzumab-treated patient with NMO. Neurol Neuroimmunol Neuroinflamm 1(3):e34. https://doi.org/10.1212/NXI.0000000000000034

    Article  PubMed  PubMed Central  Google Scholar 

  110. Paul F, Murphy O, Pardo S, Levy M (2018) Investigational drugs in development to prevent neuromyelitis optica relapses. Expert Opin Investig Drugs 27(3):265–271. https://doi.org/10.1080/13543784.2018.1443077

    Article  CAS  PubMed  Google Scholar 

  111. Ayzenberg I, Schollhammer J, Hoepner R, Hellwig K, Ringelstein M, Aktas O, Kumpfel T, Krumbholz M, Trebst C, Paul F, Pache F, Obermann M, Zeltner L, Schwab M, Berthele A, Jarius S, Kleiter I, Neuromyelitis Optica Study G (2016) Efficacy of glatiramer acetate in neuromyelitis optica spectrum disorder: a multicenter retrospective study. J Neurol 263(3):575–582. https://doi.org/10.1007/s00415-015-7991-1

    Article  CAS  PubMed  Google Scholar 

  112. Stellmann JP, Krumbholz M, Friede T, Gahlen A, Borisow N, Fischer K, Hellwig K, Pache F, Ruprecht K, Havla J, Kumpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Young KL, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker RA, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Zettl U, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C, Kleiter I, Nemos (2017) Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response. J Neurol Neurosurg Psychiatry 88(8):639–647. https://doi.org/10.1136/jnnp-2017-315603

    Article  PubMed  Google Scholar 

  113. Valentino P, Marnetto F, Granieri L, Capobianco M, Bertolotto A (2017) Aquaporin-4 antibody titration in NMO patients treated with rituximab: a retrospective study. Neurol Neuroimmunol Neuroinflamm 4(2):e317. https://doi.org/10.1212/NXI.0000000000000317

    Article  PubMed  Google Scholar 

  114. Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Wegner B, Hellwig K, Pache F, Ruprecht K, Havla J, Krumbholz M, Kumpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker R, Schwab M, Marziniak M, Then Bergh F, Hofstadt-van Oy U, Neuhaus O, Winkelmann A, Marouf W, Faiss J, Wildemann B, Paul F, Jarius S, Trebst C, Neuromyelitis Optica Study G (2016) Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol 79(2):206–216. https://doi.org/10.1002/ana.24554

    Article  CAS  PubMed  Google Scholar 

  115. Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, Shattuck DW, Hull L, Wang HJ, Elashoff RM, Swerdloff RS, Voskuhl RR (2007) Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol 64(5):683–688. https://doi.org/10.1001/archneur.64.5.683

    Article  PubMed  Google Scholar 

  116. Kurth F, Luders E, Sicotte NL, Gaser C, Giesser BS, Swerdloff RS, Montag MJ, Voskuhl RR, Mackenzie-Graham A (2014) Neuroprotective effects of testosterone treatment in men with multiple sclerosis. Neuroimage Clin 4:454–460. https://doi.org/10.1016/j.nicl.2014.03.001

    Article  PubMed  PubMed Central  Google Scholar 

  117. Gold SM, Chalifoux S, Giesser BS, Voskuhl RR (2008) Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone. J Neuroinflammation 5:32. https://doi.org/10.1186/1742-2094-5-32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Gold SM, Voskuhl RR (2016) Pregnancy and multiple sclerosis: from molecular mechanisms to clinical application. Semin Immunopathol 38(6):709–718. https://doi.org/10.1007/s00281-016-0584-y

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

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

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Manuel A. Friese.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-018-0723-8

Keywords

Navigation