Immune Imbalance in Lupus

September 9, 2016

As with most things in life, balance in the immune system is key to the prevention of disease – too little activity and one is prone to infections or the development of cancer; too much as in the case in Lupus, and a vicious cycle of inflammation and autoimmunity results.  So what is unique about how the immune system is wired in lupus and how can we harness that knowledge to help restore balance?

Overactivation of antiviral immune defenses is one of the most unique features of lupus that is thought to be central to understanding what is driving the disease. When a virus invades cells of the body our first line of defense is produce small proteins called Interferons that work to trigger an anti-viral state.  In many lupus patients, increased levels of Interferons are detectable, contributing to overactivation of the immune system and driving autoimmunity. Many new therapies are in development which target interferons and their effects – anti-interferon therapy.  Clinical trials are showing that these new drugs can reduce expression of genes turned on by interferons in lupus patients, but thus far these strategies have had little effect on reversing actual Lupus symptoms. Efforts are now focused on identifying if there are specific sub-groups of patients that are most likely to respond to these therapies.

Another unique feature of lupus is the relatively recent discovery that cells working at the frontline of our defense against infectious agents called Neutrophils, are fundamentally different in lupus patients compared to healthy individuals. Lupus neutrophils are activated more easily, and once activated release proteins and material that triggers inflammation and activates the immune system. Not only are lupus neutrophils highly inflammatory but they also produce Interferons. They have been shown to be important in both heart and kidney disease in lupus and likely to have other important associations with other organs. Working out how to reprogram or deactivate lupus neutrophils is a key focus now for researchers and holds much promise for the development of new therapies. Indeed, drugs already in development for other conditions may also be effective in working on lupus neutrophils – a very exciting new avenue of research for the fight to develop new and improved therapies.

The good news is that as we unravel what aspects of the immune system are not functioning in the way they should in lupus patients, the closer we get to developing immune-based therapies that can be used to treat or even cure the disease.

By Dr. Caroline Jefferies, Medical Researcher