Neuromyelitis optica spectrum disorders (NMOSD) predominantly affect women who are of childbearing age. Understanding the interactions between pregnancy and NMOSD is important for clinical management. Aquaporin-4 (AQP4), the most common target antigen in NMOSD, is expressed on placenta in early pregnancy. A variety of immune and cytokine changes in pregnancy may impact pregnancy outcomes in NMOSD patients. Relapses continue during pregnancy and increase in frequency postpartum. Preeclampsia and fetal loss are more frequent in NMOSD than in controls. Transfer of AQP4-immunoglobulin G (IgG) from mother to baby occurs but appears not to cause disease. Several treatment options are relatively safe and mitigate the risk of relapse during pregnancy and postpartum. For patients with active NMOSD, it may be advisable to continue immunotherapy during pregnancy.
LennonVAWingerchukDMKryzerTJet alA serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis. Lancet2004; 364: 2106–2112.
3.
PapadopoulosMCVerkmanAS.Aquaporin 4 and neuromyelitis optica. Lancet Neurol2012; 11: 535–544.
4.
Varrin-DoyerMSpencerCMSchulze-TopphoffUet alAquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize clostridium ABC transporter. Ann Neurol2012; 72: 53–64.
5.
RateladeJZhangHSaadounSet alNeuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss. Acta Neuropathol2012; 123: 861–872.
6.
WangHHDaiYQQiuWet alInterleukin-17-secreting T cells in neuromyelitis optica and multiple sclerosis during relapse. J Clin Neurosci2011; 18: 1313–1317.
7.
FlanaganEPCabrePWeinshenkerBGet alEpidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum. Ann Neurol. Epub ahead of print 17 February 2016. DOI: 10.1002/ana.24617.
8.
PanditLAsgariNApiwattanakulMet alDemographic and clinical features of neuromyelitis optica: A review. Mult Scler2015; 21: 845–853.
9.
ConfavreuxCHutchinsonMHoursMMet alRate of pregnancy-related relapse in multiple sclerosis. Pregnancy in multiple sclerosis group. N Engl J Med1998; 339: 285–291.
10.
DavoudiVKeyhanianKBoveRMet alImmunology of neuromyelitis optica during pregnancy. Neurol Neuroimmunol Neuroinflamm2016; 3: e288.
11.
SaitoSNakashimaAShimaTet alTh1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol2010; 63: 601–610.
12.
WangWJHaoCFYiLet alIncreased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol2010; 84: 164–170.
13.
SzarkaARigoJLazar Beko MolvarecLGA. Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array. BMC Immunol2010; 11: 59.
14.
TorricelliMBellisaiFNovembriRet alHigh levels of maternal serum IL-17 and activin A in pregnant women affected by systemic lupus erythematosus. Am J Reprod Immunol2011; 66: 84–89.
15.
ChiharaNAranamiTSatoWet alInterleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci U S A2011; 108: 3701–3706.
16.
BorzychowskiAMCroyBAChanWLet alChanges in systemic type 1 and type 2 immunity in normal pregnancy and pre-eclampsia may be mediated by natural killer cells. Eur J Immunol2005; 35: 3054–3063.
17.
KeyhanianKDavoudiVEtemadifarMet alBetter prognosis of multiple sclerosis in patients who experienced a full-term pregnancy. Eur Neurol2012; 68: 150–155.
18.
AirasLSarasteMRintaSet alImmunoregulatory factors in multiple sclerosis patients during and after pregnancy: Relevance of natural killer cells. Clin Exp Immunol2008; 151: 235–243.
19.
LachapelleMHMironPHemmingsRet alEndometrial T, B, and NK cells in patients with recurrent spontaneous abortion. Altered profile and pregnancy outcome. J Immunol1996; 156: 4027–4034.
20.
BourdetteDYadavV.B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. Curr Neurol Neurosci2008; 8: 417–418.
21.
PanchanathanRChoubeyD.Murine BAFF expression is up-regulated by estrogen and interferons: Implications for sex bias in the development of autoimmunity. Mol Immunol2013; 53: 15–23.
22.
NakashimaITakahashiTCreeBAet alTransient increases in anti-aquaporin-4 antibody titers following rituximab treatment in neuromyelitis optica, in association with elevated serum BAFF levels. J Clin Neurosci2011; 18: 997–998.
23.
KarpuzogluEPhillipsRAGogalRMet alIFN-gamma-inducing transcription factor, T-bet is upregulated by estrogen in murine splenocytes: Role of IL-27 but not IL-12. Mol Immunol2007; 44: 1808–1814.
24.
FengXRederNPYanamandalaMet alType I interferon signature is high in lupus and neuromyelitis optica but low in multiple sclerosis. J Neurol Sci2012; 313: 48–53.
25.
PauklinSSernandezIVBachmannGet alEstrogen directly activates AID transcription and function. J Exp Med2009; 206: 99–111.
26.
De FalcoMCobellisLTorellaMet alDown-regulation of aquaporin 4 in human placenta throughout pregnancy. In Vivo2007; 21: 813–817.
FragosoYDAdoniTBichuettiDBet alNeuromyelitis optica and pregnancy. J Neurol2013; 260: 2614–2619.
38.
HuangYWangYZhouYet alPregnancy in neuromyelitis optica spectrum disorder: A multicenter study from South China. J Neurol Sci2017; 372: 152–156.
39.
BourreBMarignierRZephirHet alNeuromyelitis optica and pregnancy. Neurology2012; 78: 875–879.
40.
ShiBZhaoMGengTet alEffectiveness and safety of immunosuppressive therapy in neuromyelitis optica spectrum disorder during pregnancy. J Neurol Sci2017; 377: 72–76.
41.
AsgariNHenriksenTBPetersenTet alPregnancy outcomes in a woman with neuromyelitis optica. Neurology2014; 83: 1576–1577.
42.
ShangWLiuJ.Neuromyelitis optica during pregnancy. Int J Gynaecol Obstet2011; 115: 66–68.
43.
ShimizuYFujiharaKOhashiTet alPregnancy-related relapse risk factors in women with anti-AQP4 antibody positivity and neuromyelitis optica spectrum disorder. Mult Scler2016; 22: 1413–1420.
RingelsteinMHarmelJDistelmaierFet alNeuromyelitis optica and pregnancy during therapeutic B cell depletion: Infant exposure to anti-AQP4 antibody and prevention of rebound relapses with low-dose rituximab postpartum. Mult Scler2013; 19: 1544–1547.
50.
GomoriEPalJAbrahamHet alFetal development of membrane water channel proteins aquaporin-1 and aquaporin-4 in the human brain. Int J Dev Neurosci2006; 24: 295–305.
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