New Hope for Lupus

Researchers from the University of Alabama at Birmingham (UAB) have discovered a new immune protein influencing autoimmune diseases such as lupus and multiple sclerosis.

In autoimmune diseases like lupus, the body’s immune system overreacts and attacks healthy tissue, instead of just eliminating germs. Lupus can affect lots of different areas of the body including the joints, skin, kidneys, lungs, heart and the brain.

The symptoms of lupus vary from person to person and can include fever, kidney trouble, feeling tired all the time and rashes. Because the effects of the disease vary so much from patient to patient, it is important to develop personalized therapies to provide people with treatment that is right for them.

The researchers behind the new study think a new mutation of an immune protein called an “Fc receptor” may help scientists develop more personalized autoimmune disease treatments.

The Fc receptor regulates the production of antibodies that attack bacteria in our bodies. Previously, scientists thought that Fc receptors could only shut down antibody production, but about 15% of the world’s population have this new kind of Fc receptor that can also activate antibody production. In people with lupus, this means that the Fc receptor would create too many antibodies, resulting in an attack on healthy cells.

Being able to identify this receptor mutation in patients could help doctors prescribe treatments specific to that patient, and it could also provide early warning signs of autoimmune disease.

Fc receptors as personalized treatment and screening tool

Dr. Robert Kimberly, director of the UAB Center for Clinical and Translational Science, who co-authored the paper, says:

“This new finding could play a significant role in the way companies design treatments for autoimmune diseases, in a more targeted approach. Now efforts can be made to target the individuals who will benefit from the treatments, based on the gene mutation.”

The efficacy of treatments for autoimmune disease is often determined by the genes that “fine-tune” the immune system of an individual. Dr. Kimberley and his team believe that identifying this new gene in patients will not only lead to faster, more appropriate treatment for patients, but will also potentially save time and money for the pharmaceutical industry.

“Our findings provide pharmaceutical companies with a new screening tool to identify not only those patients most likely to respond to these antibody-based therapies but, more importantly, individuals in which these therapies might actually be harmful,” says co-author Jeffrey Edberg, PhD.

“Such an approach may save not only time but also costs associated with clinical trials by identifying patients with this mutation,” he adds.

How can awareness of this mutation improve existing treatments?

Approximately a third of autoimmune disease patients do not respond to the traditional antibody-based treatments. These drugs work by targeting one protein - tumor necrosis factor alpha – known to inflame autoimmune conditions.

A rash caused by lupus
An example of a rash caused by lupus.

Newer therapies aim to decrease the activity of B cells, the cells that create antibodies. However, these treatments may not be effective for people who have the Fc receptor variant.

“The problem for drug designers is that they have been designing antibody-based drugs with an understanding of B cell biology made out of date by our study – a world where only inhibitory feedback Fc receptors are signaling,” Kimberly says.

Edberg agrees that pharmaceutical manufacturers need to re-evalute their areas of development:

“With advances in genetics, the pharmaceutical industry now has knowledge available to identify the patients most likely to respond to these therapies, and become a leader in the developing field of personalized medicine.”

The researchers speculate that the same overreactive immune system that makes people who have this Fc receptor variant more likely to get lupus may hold the key for effective treatment of the same individuals.

“Future research into the impact of expression of this Fc receptor in B cells on antibody production in both health and disease will likely lead to advances in our understanding of both autoimmunity and natural responses to infectious disease challenges,” says Dr. Kimberly.

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