Understanding How Our Greatest Ally Can Also Be Our Greatest Foe

Achoo…sniffle sniffle…cough…hack…These sounds echoing throughout the office herald the arrival of yet another cold/flu season. Yay! But before you convince yourself to work from behind the barricades of your home, remember that we do have a wonderful defense: our immune system. When it works properly, everything is right with the world. However, it can also go very wrong.

The scientific literature is peppered with examples of how our immune system defender can turn on us, such as in the case of rheumatoid arthritis. In your joints, the synovium provides critical lubrication, akin to the oil needed to keep the engine parts running smoothly in cars (Mayo Clinic, 2017a). In rheumatoid arthritis, the immune system starts attacking this tissue, causing unnecessary inflammation where it does not belong. Without treatment, the inflammation persists, the pain worsens and the joints become disfigured and even inoperable.

New research is highlighting many additional, even surprising instances in which our immune system ally can seem to turn on us. Trisomy 21, the inclusion of an additional chromosome 21, leads to Down Syndrome (DS) and its wide spectrum of complications (Mayo Clinic, 2017b). To understand how an extra chromosome can lead to such a diverse set of complications, researchers measured changes in blood proteins to try to understand what is happening at a deeper level. From their findings, they learned that the extra 21st chromosome can lead to “profound” protein changes in the immune system (Sullivan et al., 2017). Interestingly, they saw dramatic increases in DS individuals of the inflammatory TNF-a signaling pathway (a target for some rheumatoid arthritis medications) (Rau, 2002; Sullivan et al., 2017), in addition to many other immune system-related proteins. More work is needed to pinpoint how these protein changes can affect various DS complications. However, it is tantalizing to think that medications aimed at treating rheumatoid arthritis may also potentially benefit DS individuals in some way.

Another surprising instance of our friend the immune system causing chaos may be premature labor. Researchers noted that a mother-to-be’s immune system changes during pregnancy to allow the fetus to grow without being attacked (Aghaeepour et al., 2017). When they investigated blood samples from pregnant women, they mapped out a clear-cut timeline of changes to the immune system. If the strict schedule is not followed, the researchers hypothesize it could be the prelude to premature labor. If this hypothesis plays out, it could yield beneficial diagnostics that could warn doctors and the mom-to-be ahead of time and result in an increase in happier birth stories.

It really does seem that a legitimate way to describe our immune system is to call it our greatest frenemy. (Hopefully, this does not bring back any painful middle school memories.) With continuing advances in diagnostics and therapeutics, we might be able to determine when the relationship turns adversarial, and take the necessary steps to mend that break. Hopefully, the friendship is mended before we need our ally the most. Goodness…I just heard another cough!

 

 References

Aghaeepour, N., Ganio, E. A., McIlwain, D., Tsai, A. S., Tingle, M., Van Gassen, S., . . . Gaudilliere, B. (2017). An immune clock of human pregnancy. Sci Immunol, 2(15). doi:10.1126/sciimmunol.aan2946

Mayo Clinic. (2017a). Rheumatoid arthritis – Symptoms and causes. Retrieved on December 8, 2017 at https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648.

Mayo Clinic. (2017b). Down syndrome – Symptoms and causes. Retrieved on December 8, 2017 at https://www.mayoclinic.org/diseases-conditions/down-syndrome/symptoms-causes/syc-20355977

Rau, R. (2002). Adalimumab (a fully human anti-tumour necrosis factor alpha monoclonal antibody) in the treatment of active rheumatoid arthritis: the initial results of five trials. Ann Rheum Dis, 61 Suppl 2, ii70-73.

Sullivan, K. D., Evans, D., Pandey, A., Hraha, T. H., Smith, K. P., Markham, N., . . . Blumenthal, T. (2017). Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation. Sci Rep, 7(1), 14818. doi:10.1038/s41598-017-13858-3