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Immunology of neuromyelitis optica during pregnancy.

Neurol Neuroimmunol Neuroinflamm. 2016 Oct 7;3(6):e288. eCollection 2016.

Davoudi V, Keyhanian K, Bove RM, Chitnis T.

Abstract

Anti-aquaporin-4 (AQP4) autoantibody plays a key role in the pathogenesis of neuromyelitis optica (NMO). Studies have shown increased relapse rates in patients with NMO during pregnancy and postpartum. High estrogen levels during pregnancy can increase activation-induced cytidine deaminase expression, which is responsible for immunoglobulin production. Additionally, sex hormones may influence antibody glycosylation, with effects on antibody function. Estrogen decreases apoptosis of self-reactive B cells, through upregulation of antiapoptotic molecules. Furthermore, high estrogen levels during pregnancy can boost B-cell activating factor and type 1 interferon (IFN) production, facilitating development of self-reactive peripheral B cells in association with increased disease activity. Elevated levels of estrogen during pregnancy decrease IFN-γ generation, which causes a shift toward T helper (Th) 2 immunity, thereby propagating NMO pathogenesis. Women with NMO have an elevated rate of pregnancy complications including miscarriage and preeclampsia, which are associated with increased Th17 cells and reduction of T-regulatory cells. These in turn can enhance inflammation in NMO. Increased regulatory natural killer cells (CD56-) during pregnancy can enhance Th2-mediated immunity, thereby increasing inflammation. In the placenta, trophoblasts express AQP4 antigen and are exposed to maternal blood containing anti-AQP4 antibodies. Animal models have shown that anti-AQP4 antibodies can bind to AQP4 antigen in placenta leading to complement deposition and placental necrosis. Reduction of regulatory complements has been associated with placental insufficiency, and it is unclear whether these are altered in NMO. Further studies are required to elucidate the specific mechanisms of disease worsening, as well as the increased rate of complications during pregnancy in women with NMO.

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LoriJC17 says:

I would like to leave a positive note for any female researching this topic.
I was diagnosed with NMO in Sept 2010. In the hospital with many symptoms including relying on use of a walker and being discharged with a cane.
I was 28, not married and no kids.
So for a young female looking ahead I was quite concerned what my future would hold as far as having kids would go and if that was any longer an option. My neurologist was very against me getting pregnant and all the research I found was very discouraging.
I was married 1 year after my diagnosis (Oct 2011) and pregnant with my first baby 5 months after that (March 2012). I was on Imuran through the pregnancy and felt great!! After I had my baby I DID get toxicity and realized after having the baby I was having some of those symptoms towards the end of my pregnancy as well. It wasn’t till a little over a year since the birth that I had my next relapse (3yrs 3mo since my initial diagnosis). I was pregnant again with my second Oct 2015, still on just Imuran. I DID miscarry once in between the two (July 2015), which can happen with health woman. A healthy baby girl was born June 2015, my next relapse was end of Feb 2016 and again Dec 2016. Whether it was pregnancy related, stress, lack of sleep I don’t know. But I know I was advised against the pregnancy and now have two beautiful, healthy children one almost 2 and one 4 1/2.
I hope this helps any women looking for hope out there or any doctor looking for information on pregnancy with NMO.

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