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
No comments:
Post a Comment