Sunday, October 6, 2013

Caution Females with NMO: NMO-IgG and You!

Our immune system is absolutely extraordinary, and to an extent, even dangerous. Our bodies target antigens, foreign bodies, by activating the immune system’s plasma cells to produce antibodies that can eventually target the antigen. After successful binding to the target antigen, the antibody can trigger additional responses that will further lead to the destruction of the antigen. Though our immune system is our main line of defense, there are times when what aids us, undergoes changes and becomes not only dangerous, but even life threatening. Although a rather common problem that is seen in immunocompromised patients, where our own body’s defenses act against us, this study focused on the effect that Neuromyelitis Optica induced antibodies, NMO-IgG, would have on women of child rearing age.1
Neuromyelitis Optica is an inflammatory, demyelinating disease of the Central Nervous System. The disease causes the presence of NMO-IgG, which is a class of circulating antibodies that researchers found bind to the main water channel protein, aquaporin-4.2 SO WHAT?

Well it turns out that when NMO-IgG binds to the aquaporin-4, it triggers a human complement, which in turn causes an inflammatory response3. However, the researchers found that there is a high concentration of aquaporin-4 channels in the fetoplacental unit, and wanted to see the effects of NMO-IgG binding to these channels. The concentration of aquaporin channels greatly increases during the second trimester, if the NMO-IgG – human complement complex shows high affinity bonding, then not only will aquaporin-4 autoimmunity be seen outside the CNS, but it could prove beneficial to pregnant women with NMO to see in what ways they can protect themselves.  

To test NMO-IgG binding in placental aquaporin-4, researchers injected NMO-IgG into pregnant mice, and tagged the antibody with a fluorophore that will shine when it binds to aquaporin-4. Not only did the NMO-IgG bind to the placental aquaporin-4, but it also triggered the classical complement pathway, causing the activation of membrane attack complexes. The antibodies in our bodies are supposed to target and destroy antigens, yet NMO-IgG has a certain mutation that causes it to target placental aquaporin-4 and thus focuses an attack once it binds to its target.

The data showed a decrease in mice pups after injecting the mothers with NMO-IgG, and a high concentration of NMO-IgG/aquaporin-4 bonding. In addition, researchers used certain NMO-IgG inhibitors to see if the antibody-aquaporin complex could still be triggered. Through the use of the inhibitor, aquaporumab, the study showed that mice pups increased due to the aquaporumab binding to the NMO-IgG inhibitor, and showing evidence that the aquaporins found in the placenta of women may be at risk to the NMO-IgG antibody1. Continued and more expansive research can be carried out to further test the aggressiveness and possibly the concentration limits and amount of NMO-IgG and its complement in attacking the aquapore-4 protein.

This research adds further light to the mysteries of our own cellular processes. Our own antibodies are mutated and then activate complexes that end up hurting ourselves. To conclude, the researchers showed that NMO-IgG can bind to placental aquporin-4, and trigger an immune response that can cause potential miscarriages. With this information, further development and studies can be seen as to what is occurring in the antibody that triggers the human complement to destroy the water channel.

Sridhar, Saranya et. al. Cellular Immune Correlates of Protection Against Symptomatic Pandemic
Influenza. 22 September 2013. Nature Medicine. Online Publication.
Primary Reference:

1.)   Saadoun, Samira et. al. “Neuralmyelitis Optica IgG Causes Placental Inflammation and Fetal Death.” September 15, 2013. Journal of Immunology. 191:2999-3005.

Secondary References

2.)   Papadopoulos, M. C., and A. S. Verkman. 2012. Aquaporin 4 and neuromyelitis optica. Lancet Neurol. 11: 535–544.

3.)   Bradl, M., T. Misu, T. Takahashi, M. Watanabe, S. Mader, M. Reindl, M. Adzemovic, J. Bauer, T. Berger, K. Fujihara, et al. 2009. Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo. Ann. Neurol. 66: 630– 643.

By Sam Davalos

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